Publication for Rag1 and Rag2

Species Symbol Function* Entrez Gene ID* Other ID Gene
coexpression		 CoexViewer
mmu Rag1 recombination activating 1 19373 [link]
mmu Rag2 recombination activating gene 2 19374

Pubmed ID Priority Text
28213501 0.99 Rag1 and Rag2, causing downregulation of both Rag1 and Rag2 mRNA but only Rag1 protein.
0.98 Rag1/Rag2 (RAG) endonuclease engage this DDR to modulate transcription of genes that regulate lymphocyte-specific processes.
0.98 Rag1 and Rag2 mRNA levels in primary pre-B cells, pro-B cells, and pro-T cells, indicating that inhibition of Rag1 and Rag2 expression is a prevalent DSB response among immature lymphocytes.
0.98 RAG1, RAG2, RSSs, or NHEJ factors that impair lymphocyte development, restrict AgR gene repertoires, and cause fatal severe combined immunodeficiency.
0.98 Rag1 and Rag2 transcription and signal differentiation of gammadelta T cells.
0.98 Rag1 and Rag2 mRNA and Rag1 protein, as well as mRNA and protein levels of Gadd45alpha, which had been shown to signal Rag1 and Rag2 transcription in a pre-B cell line.
0.98 Rag1 mRNA were reduced by more than 50% at 1 and 4 hours after exposure to 10 Gy of ionizing radiation, while levels of Rag2 mRNA were reduced by ~50% at both times (Fig. 1A), indicating that immature B lymphocytes rapidly inhibit Rag1 and Rag2 expression in response to IR.
0.98 Rag1 and Rag2 mRNA each were increased by ~40% at 4 hours after exposure to 10 Gy of ionizing radiation (Fig. 1B).
0.98 Rag1 and Rag2 expression in developing B lymphocytes but not developing T lymphocytes.
0.98 Rag1-/- and Rag2-/- mice suggest that DSBs downregulate Rag1 and Rag2 expression in primary pro-B and pro-T cells.
0.98 Rag1 and Rag2 mRNAs
0.98 Rag1 and Rag2 expression, we turned to the ex vivo culture system wherein we discovered that RAG DSBs inhibit Rag1 and Rag2 expression.
0.98 Rag1 and Rag2 transcription.
0.98 Rag1 and Rag2 mRNA each were reduced ~80% at 1 and 4 hours following exposure to ionizing radiation (Fig. 2A), indicating that pre-B cells rapidly inhibit Rag1 and Rag2 expression in response to IR.
0.98 Rag1 and Rag2 mRNA each were reduced ~60-80% at 1 and 4 hours with treatment with bleomycin (Fig. 2B), indicating that DSBs induced in pre-B cells rapidly inhibit Rag1 and Rag2 expression.
0.98 Rag1 and Rag2 mRNA each were reduced ~80% at 1 and 4 hours with treatment with etoposide (Fig. 2C), indicating that DSBs induced in pre-B cells rapidly inhibit Rag1 and Rag2 expression.
0.98 Rag1 and Rag2 mRNA levels, we conclude that any type of DSB activates DSB-induced feedback inhibition of Rag1 and Rag2 expression.
0.98 Rag1 and Rag2 expression to suppress V(D)J recombination, Rag1 and/or Rag2 protein levels must be diminished as a result of decreased Rag1 and Rag2 mRNA.
0.98 Rag1 and Rag2 are required for RAG endonuclease activity, the downregulation of Rag1 protein levels in response to the induction of DSBs could be sufficient to inhibit V(D)J recombination.
0.98 Rag1 and Rag2 mRNAs in irradiated pre-B cells (Fig. 3A), the kinetics and extents by which EU-labeled Rag1 and Rag2 mRNAs are lost in irradiated cells suggests that DSBs cause an immediate halt of Rag1 and Rag2 transcription.
0.98 Rag1 and Rag2 transcription is specifically targeted by the DDR, and not simply part of a generalized inhibition of transcription in the presence of widespread DNA damage.
0.98 Rag1 and Rag2 transcription through factors constitutively expressed in primary pre-B cells.
0.98 Rag1 and Rag2 transcription being the predominant mechanism by which pre-B cells signal DSB-induced loss of Rag1 and Rag2 expression.
0.98 Rag1 and Rag2 expression.
0.98 Rag1 and Rag2 mRNAs in non-irradiated cells treated with KU55933 versus vehicle only (Fig. 4A), likely reflecting ATM-dependent suppression of Rag1 and Rag2 transcription from DSBs induced by RAG during Igkappa recombination and by other transcription and cellular metabolites.
0.98 Rag1 and Rag2 mRNAs compared to EmuBCL2 pre-B cells (data not shown), possibly reflecting ATM-dependent inhibition of Rag1 and Rag2 expression from DSBs.
0.98 Rag1 and Rag2 mRNA from 1-4 hours after irradiation of pre-B cells that lack ATM indicates that IR-induced DSBs signal through ATM to downregulate Rag1 and Rag2 expression.
0.98 Rag1 and Rag2 expression (compare Fig. 3B and Supplemental Fig. 2B).
0.98 Rag1 and Rag2 expression in pre-B cells, with the absence of Nemo resulting in slower kinetics by which pre-B cells downregulate Rag1 and Rag2 expression upon irradiation.
0.98 Rag1 and Rag2 transcription in response to DSBs: an early initiation phase that is partially dependent on Nemo and a later maintenance phase that requires Nemo expression.
0.98 Rag1 and Rag2 expression and inhibit V(D)J recombination in response to DNA damage.
0.98 Rag1 and Rag2 mRNA levels following ionizing radiation is a response shared by pro-T, pro-B, and pre-B cells.
0.98 Rag1 and Rag2 expression.
0.98 Rag1 and Rag2 expression.
0.98 Rag1 and Rag2 protein are required for RAG endonuclease activity, DSBs induced in pre-B cell lines by etoposide inhibit recombination of endogenous Igkappa loci and a chromosomally integrated artificial substrate.
0.98 Rag1 and Rag2 mRNAs and Rag1 protein and to feedback inhibit additional RAG cleavage of Igkappa gene segments.
0.98 Rag1 and Rag2 transcription, leading to rapid downregulation of Rag1 protein expression and thereby V(D)J recombination throughout the nucleus.
0.98 Rag2 protein in thymocytes harboring RAG DSBs at TCR loci may result from a long half-life of endogenous Rag2 protein enabling Rag2 to persists following DSB-induced repression of Rag1/Rag2 transcription and resultant loss of Rag1 protein.
0.98 Rag1 and Rag2 mRNA levels in primary pre-B cells implicates a role for canonical NF-kappaB transcription factors.
0.98 Rag1/Rag2 transcription.
0.98 Rag1/Rag2 locus, including the ERag B cell specific enhancer and the D3 lymphoid specific enhancer, with BCR activation increasing p65 and c-Rel binding and decreasing p50 binding.
0.98 Rag1 and Rag2.
0.98 Rag1 and Rag2 transcription in pre-B cells, with increased binding of p50 in response to DSBs repressing Rag1/Rag2 transcription.
0.98 Rag1/Rag2 locus.
0.98 Rag1/Rag2 expression in pre-B cells through ATM-FOXO1 signaling.
0.98 Rag1/Rag2 transcription.
0.98 Rag1 and Rag2 expression, but we also show that this DSB response occurs independent of new protein synthesis and involves transcriptional repression of the Rag1/Rag2 locus.
0.98 Rag1 and Rag2 expression in pre-B cells, with the absence of Nemo possibly resulting in slower kinetics by which pre-B cells suppress Rag1 and Rag2 expression in response to DSBs.
0.98 Rag1 and Rag2 expression in response to DSBs.
0.98 Rag1 and Rag2 expression in response to DSBs would be unique among the types of immature B and T cells that assemble AgR genes.
0.98 Rag1 and Rag2 expression, providing additional support for our model wherein the responses of these immature lymphocytes to RAG DSBs is one essential mechanism for enforcing AgR allelic exclusion.
0.98 Rag1 and Rag2 contain SQ/TQ motifs that could be phosphorylated by ATM and/or the related DNA-PK protein kinase.
0.98 Rag1 to enhance the endonuclease activity of RAG1/RAG2 complexes, it is conceivable that ATM phosphorylation of Rag1 and/or Rag2 directly suppresses the ability of RAG to bind and/or cleave DNA.
0.98 Rag2 protein in response to DSBs opens the possibility that ATM might regulate the subcellular location of Rag1 protein.
0.98 Rag1 and Rag2 expression in response to ionizing radiation.
0.98 Rag1 and Rag2 mRNA and Rag1 protein.
0.98 Rag1 and Rag2 transcription.
0.98 Rag1 and Rag2 expression.
0.98 Rag1 and Rag2 expression in response to DSBs.
0.97 Rag1 and Rag2 Transcription and V(D)J Recombination in Response to DNA Double Strand Breaks
0.97 Rag1 and Rag2 transcription and drive differentiation of conventional B and alphabeta T cells.
0.97 Rag1 and Rag2 mRNA.
0.97 Rag1 and Rag2 mRNA in response to ionizing radiation is a prevalent response of immature lymphocytes
0.97 Rag1 and Rag2 mRNA in BM but not thymuses of wild-type mice that lack the pro-survival EmuBCL2 transgene (Fig. 1C, D).
0.97 Rag2 mRNA in BM and thymus of Rag1-/- mice to a similar extent as Rag1 mRNA in Rag2-/- mice.
0.97 Rag1 and Rag2 transcription.
0.97 Rag1 and Rag2 in an immortalized mouse pre-B cell line, our findings supported a model wherein DSBs suppress Rag1 and Rag2 transcription through ATM-mediated downregulation of Gadd45alpha mRNA.
0.97 Rag1 and Rag2 mRNAs following irradiation of primary pre-B cells cultured from VavCre+Tp53flox/flox mice with hematopoietic lineage-specific deletion of Tp53 (Supplemental Fig. 2E).
0.97 Rag1 and Rag2 and recombine Igkappa loci.
0.97 Rag1 and Rag2 for several days.
0.97 Rag1 and Rag2 mRNA and upregulation of p21 mRNA (Fig. 6A).
0.97 Rag1 and Rag2 mRNA and upregulation of p21 mRNA (Fig. 6C).
0.97 Rag1/Rag2 expression in immature B cells, reaching apparently contradictory conclusions.
0.97 Rag1 and Rag2 expression through other Nemo-mediated signaling pathways.
0.97 Rag1/Rag2 transcriptional repression, while ATM-Nemo signaling maintains this response.
0.97 Rag1/Rag2 expression, such as by persisting longer after cessation of ATM kinase activity following DSB repair.
0.97 Rag1 and Rag2 mRNA levels in pro-B cells, pre-B cells, and pro-T cells, but not in total thymocytes, have important implications for mechanisms by which immature lymphocytes regulate V(D)J recombination.
0.97 Rag1/Rag2 transcription in response to DSBs.
0.97 Rag1 and/or Rag2 protein might inactivate RAG endonuclease activity prior to the reduction of Rag1 protein levels.
0.96 Rag1 and Rag2 expression in developing B and T lymphocytes.
0.96 Rag1 and Rag2 expression, they cannot rule out that other types of cellular damage caused by IR promote this response.
0.96 Rag1 and Rag2 mRNAs and/or repression of Rag1 and Rag2 transcription.
0.96 Rag1and Rag2 transcriptional suppression, inhibition of new protein synthesis by cycloheximide treatment does not prevent the loss of Rag1 and Rag2 mRNA levels following irradiation of EmuBCL2 pre-B cells (Fig. 3C).
0.96 Rag1 and Rag2 expression (Supplemental Fig. 2C).
0.96 Rag1 and Rag2 expression requires the NF-kappaB essential modulator protein
0.96 Rag1 and Rag2 expression, we sought to test our hypothesis that these types of DSBs inhibit V(D)J recombination.
0.96 Rag1 and Rag2 expression and/or Jkappa recombinational accessibility.
0.96 Rag1/Rag2 expression depending on the lines analyzed.
0.95 Rag1 and Rag2 expression in response to DSBs.
0.95 Rag1 mRNA in BM from irradiated Rag2-/- mice relative to BM from non-irradiated Rag2-/- mice (Fig. 1E).
0.95 Rag1 mRNA in Rag2-/- thymuses were reduced ~40% at 1 and 4 hours after 10 Gy IR.
0.95 Rag1 and Rag2 for several days after IL7 removal.
0.95 Rag1 and Rag2 mRNA.
0.95 Rag1 and Rag2 expression following the induction of DSBs in primary pre-B cells.
0.95 Rag1 and Rag2 mRNA in Mb1Cre+Nemoflox/floxEmuBCL2 pre-B cells at 1 hour following IR is to a lesser extent than in EmuBCL2 pre-B cells (Fig. 5B).
0.95 Rag1/Rag2.
0.95 Rag1 and Rag2 proteins in DSB-induced inhibition of V(D)J recombination.
0.94 Rag1 and Rag2 mRNA loss in response to IR, one would predict appreciable decreased levels of Rag1 and Rag2 protein at 1 hour after irradiation.
0.94 Rag1 and Rag2 mRNA following irradiation (Fig. 4A).
0.94 Rag1 and Rag2 mRNA levels, it will be important to assess whether intrinsic features of the RAG proteins or the location, proximity, of structures of the two DSBs induced by RAG during Igkappa recombination amplify DDR signaling.
0.93 Rag1 mRNA in Rag2-/- BM were reduced ~75% at 1 hour after 10 Gy IR and ~90% at 4 hours after 10 Gy IR.
0.93 Rag1 and Rag2 mRNA and higher levels of p21 mRNA in irradiated EmuBCL2 pre-B cells as compared to non-irradiated EmuBCL2 pre-B cells (Fig. 2A).
0.93 Rag1 and Rag2 expression requires the ATM kinase
0.93 Rag1 and Rag2 and recombine Igkappa loci.
0.93 Rag1 and Rag2 expression, flow cytometry analysis revealed that etoposide suppressed generation of GFP+ cells (Fig. 6F).
0.93 Rag1 monomers than Rag2 monomers, DSB-induced downregulation of Rag1 protein in immature lymphocytes would be predicted to be a more effective way to reduce RAG activity than downregulation of Rag2 protein.
0.93 Rag1/Rag2 transcription or dominant roles of cis-regulatory elements that drive transcription of Rag1 and Rag2 in pre-T cells.
0.92 Rag1 and Rag2 mRNA levels, even after IL7 withdrawal.
0.91 Rag1 and Rag2 mRNAs and higher levels of p21 mRNA in EmuBCL2 pre-B cells treated with etoposide relative to EmuBCL2 pre-B cells treated with only vehicle (Fig. 2C).
0.91 Rag1 and Rag2 mRNA levels at 4 hours following IR were equivalent to unirradiated cells, the levels at 1 hour after IR were decreased as compared to unirradiated cells (Fig. 5A).
0.91 Rag1 but not Rag2.
0.91 Rag1/Rag2 transcription should be assessed to distinguish a cause-effect relationship versus another unlinked ATM-dependent correlation.
0.90 Rag1 and Rag2 mRNAs and higher levels of p21 mRNA in BM from irradiated EmuBCL2 mice as compared to BM from non-irradiated EmuBCL2 mice (Fig. 1A).
0.90 Rag1 and Rag2 mRNAs and higher levels of p21 mRNA in EmuBCL2 pre-B cells treated with bleoymcin relative to EmuBCL2 pre-B cells treated with only vehicle (Fig. 2B).
0.90 Rag1 and Rag2 mRNA and higher levels of p21 mRNA after an additional 48 hours of culture (Fig. 6E).
0.89 Rag1/Rag2 transcription, major obstacles exist for testing these models.
0.88 Rag1 and Rag2 expression.
0.87 Rag1 or Rag2 mRNA in thymuses from irradiated EmuBCL2 mice relative to thymuses from non-irradiated EmuBCL2 mice, despite induction of DSBs as reflected by elevated p21 mRNA levels (Fig. 1B).
0.86 Rag1 and Rag2 expression during culture, a small fraction (~10%) of EmuBCL2-pINV cells expresses GFP before the addition of STI571.
0.84 Rag1 and Rag2 suppression does not depend on suppression of Gadd45alpha expression
0.83 Rag1 protein but not Rag2 protein
0.81 Rag1 and Rag2 mRNAs in irradiated cells relative to non-irradiated cells (Fig. 3B).
0.75 Rag1 mRNA in thymuses from irradiated Rag2-/- mice as compared to thymuses from non-irradiated Rag2-/- mice (Fig. 1F).
0.74 Rag1 and Rag2 expression in primary pro-B and pro-T cells.
0.72 Rag1/Rag2 expression should open paths forward.
0.57 Rag1 and Rag2 transcription in response to DSBs, our experiments do not address the possibility for inactivation of Gadd45alpha protein activity by post-translational modifications or other mechanisms.
0.53 Rag1 and Rag2 transcription because they are directly induced to die.
25847946 0.98 Rag1 and Rag2 gene promoters in double-positive thymocytes and that SATB1 is a regulator of Rag locus organization in these cells.
0.98 Rag1 and Rag2 gene expression in CD4+CD8+ double-positive (DP) thymocytes depends on the activity of a distant anti-silencer element (ASE) that counteracts the activity of an intergenic silencer.
0.98 Rag1 and Rag2 gene promoters in DP thymocytes, bringing the two promoters together to form an active chromatin hub.
0.98 Rag1 and Rag2 at the DP stage.
0.98 Rag2 in the chromatin hub and the loading of RNA polymerase II to both the Rag1 and Rag2 promoters.
0.98 RAG1 and RAG2), which can recognize and cleave at recombination signal sequences (RSSs) that flank TCR and immunoglobulin V, D, and J gene segments.
0.98 Rag1 and Rag2 genes display a distinctive, tightly linked genomic organization with stringently and coordinately regulated expression during T and B lymphocyte development.
0.98 Rag1 and Rag2 promoters.
0.98 Rag1 and Rag2 genes, which can extinguish Rag expression in DP thymocytes and partially suppress expression in DN thymocytes.
0.98 Rag1 and Rag2 at the DP stage.
0.98 Rag2 into this complex and to load RNA polymerase II (RNA pol II) to the Rag1 and Rag2 promoters.
0.98 Rag1 and Rag2 promoters and gene bodies in Satb1f/fVav-Cre DP thymocytes (sites L, M, O and P, Fig. 2 C).
0.98 Rag1 and Rag2 promoter regions in DP thymocytes (Fig. 3 A).
0.98 Rag1 and Rag2 promoters.
0.98 Rag1 and Rag2 promoters, perhaps functioning as a classical enhancer.
0.98 Rag1 and Rag2 promoters and brings these promoters together to form a chromatin hub in DP thymocytes (Fig. 8), and it can directly and potently activate the Rag1 and Rag2 promoters in the absence of the silencer or any other locus elements.
0.98 Rag1 and Rag2 promoters was only detected in SATB1-sufficient DP thymocytes, thereby correlating with looping between the ASE and the two Rag promoters.
0.98 Rag2 promoter interactions with the ASE and Rag1 promoter, and in RNA pol II occupancy at the Rag promoters and silencer in DP thymocytes (Fig. 8).
0.98 Rag1 promoter interactions can be assembled in a SATB1-independent fashion, but that the Rag2 promoter depends on SATB1 to effectively join this complex (Fig. 8).
0.98 Rag2 in the absence of SATB1 may be a straightforward consequence of exclusion of this promoter from the ASE-Rag1 complex.
0.97 Rag1 and Rag2 (hereafter, Rag) gene expression during T and B lymphocyte development.
0.97 Rag1 and Rag2 expression by two orders of magnitude in DP thymocytes and prevented differentiation into SP cells, but had only modest effects on Rag gene expression in DN thymocytes.
0.97 Rag1 and Rag2 expression at the DN stage but displayed ~70 and 80% reductions in Rag1 and Rag2 expression, respectively, in DP thymocytes.
0.97 Rag1 and Rag2 transcripts were observed in DP thymocytes from Satb1f/fLck-Cre mice; thus, the Rag expression defect is T cell intrinsic (Fig. 2 B).
0.97 Rag1 promoter fragment as a viewpoint, we detected an interaction between the Rag1 and Rag2 promoters in WT DP thymocytes and found this interaction to be substantially diminished in ASE-/- DP thymocytes (Fig. 5 A).
0.97 Rag1 and Rag2 promoters in DP thymocytes, and that efficient tethering of the Rag2 promoter depends on SATB1.
0.97 Rag1 and Rag2 promoters in WT DP thymocytes (sites L and Q, Fig. 6 A).
0.97 Rag1 and Rag2 promoters.
0.97 Rag1 and Rag2 promoters acquire high levels of RNA pol II when they are tethered to each other and to the ASE.
0.97 Rag1 and Rag2 promoters drove minimal luciferase expression compared with positive control plasmids containing the promoters plus the Tcra enhancer (Ealpha), a potent enhancer in DP thymocytes.
0.97 Rag1 and Rag2 promoters have minimal contact with the RNA polII-loaded ASE in DN thymocytes and are transcribed at modest levels.
0.97 Rag1 and Rag2 promoters.
0.96 Rag1 and Rag2 gene expression during thymocyte development
0.96 Rag1 and Rag2 gene expression to be <1% of the level in WT DP thymocytes, suggesting a more dramatic expression defect than in Satb1f/fVav-Cre mice.
0.96 Rag2, and within the Rag2 and Rag1 gene bodies (Fig. 3, B and C).
0.96 Rag1-Rag2 promoter interactions were reduced partially in Satb1f/fVav-Cre DP thymocytes (Fig. 5, A and B).
0.96 Rag1 and Rag2 promoters in extrachromosomal luciferase reporters that lack the silencer.
0.95 Rag2 but not the Rag1 promoter with the ASE in Satb1f/fVav-Cre DP thymocytes (Fig. 5, A and B), a finding consistent with 3C analyses from the ASE viewpoint (Figs. 3 and 4).
0.94 Rag1 and Rag2 expression were higher in DP thymocytes than in DN3 thymocytes from WT mice.
0.93 Rag2 promoter interaction but normal ASE-Rag1 promoter interaction in Satb1f/fVav-Cre DP thymocytes (Fig. 4, A and B).
0.92 Rag1 and Rag2 promoters.
0.90 Rag1 and Rag2 gene expression in SATB1-deficient DP thymocytes
0.90 Rag1 and Rag2 promoters 70-100 kb away (Fig. 3 B).
0.89 Rag1 and Rag2 promoters.
0.85 Rag1 and Rag2 gene expression in SATB1-deficient and ASE-deleted DP thymocytes.
0.85 Rag1 and Rag2 promoter-driven luciferase reporter constructs in transiently transfected cells.
0.73 Rag1 and Rag2 promoters
0.72 Rag1 and Rag2 promoters.
0.65 Rag1 and Rag2 genes and known cis-regulatory elements ASE, Erag (enhancer of Rag), D3 (distal enhancer), Ep (enhancer proximal), and Sil (silencer).
0.53 Rag1 and Rag2 gene expression in DP thymocytes.
30545902 0.98 Rag1 and Rag2 is tightly regulated in developing T cells to mediate TCR gene assembly.
0.98 Rag1 and Rag2 gene expression in CD4+CD8+ thymocytes depends on Rag1 and Rag2 promoter activation by a distant antisilencer element (ASE).
0.98 Rag2 recruitment and expression dependent on assembly of a functional ASE-Rag1 framework.
0.98 Rag1 and Rag2 promoters to be coordinately controlled by additional cis-regulatory elements that differ between B and T cells.
0.98 Rag1 and Rag2 promoters.
0.98 Rag1 and Rag2 promoters in T cells, but it is not known if they do so by direct binding.
0.98 Rag1 and Rag2 promoters.
0.98 Rag1 promoter directly induce Rag1 gene expression and indirectly induce Rag2 gene expression.
0.98 Rag1 and Rag2 gene expression was dramatically suppressed by the absence of Runx1 or GATA3 and was partially suppressed by the absence of E2A (encoded by Tcf3; Fig. 5 B).
0.98 Rag1 and Rag2 promoters interact in a developmental stage-specific fashion in DP thymocytes and that these interactions are mediated, in part, by chromatin organizer SATB1.
0.98 Rag1 promoter is essential to recruit or maintain Rag2 promoter contacts with the Rag1 promoter and the ASE (Fig. 6 C).
0.98 Rag1 promoter interaction creating a framework that allows stable Rag2 promoter recruitment to form a three-way complex.
0.98 Rag1 and Rag2 gene expression in VL3-3M2 DP thymocytes and that Ikaros functions in part by mediating disassembly of the RAG locus chromatin hub.
0.98 Rag1 and Rag2 promoters in direct physical interactions to form an active chromatin hub.
0.98 Rag1 expression was elevated in Rag2 promoter deleted VL3-3M2 cells, suggesting that recruitment of Rag2 into the ASE-Rag1 promoter complex may result in competition between the two promoters for the binding of certain transcriptional regulators.
0.98 Rag1 promoter and the ASE in DP thymocytes; binding was detected at the Rag2 promoter as well (Gene Expression Omnibus accession no. GSE61148).
0.97 Rag1 and Rag2) form a heterotetrameric RAG recombinase complex that recognizes and cleaves DNA at recombination signal sequences flanking variable (V), diversity (D), and joining (J) gene segments of antigen receptor loci to initiate the V(D)J recombination reaction.
0.97 Rag1 and Rag2 is tightly controlled in a cell- and developmental stage-specific manner.
0.97 Rag2 promoter dependent on assembly of a functional ASE-Rag1 promoter framework.
0.97 Rag1 promoter mutations ablate Rag2 gene expression due to diminished contacts between the Rag2 promoter and both the ASE and Rag1.
0.97 Rag1 and Rag2 genes (Fig. 2 E).
0.97 Rag1 and Rag2 promoters, as did VL3-3M2 cells lacking SATB1 (Fig. 6 D).
0.97 Rag1 promoter interaction may represent the fundamental building block of locus organization and may serve as a platform for Rag2 promoter recruitment.
0.96 Rag1 and Rag2 promoters were potently activated by the wild-type ASE (Fig. 1 D).
0.96 Rag1 and Rag2 transcripts as compared with control cells treated with the DMSO vehicle (Fig. 7 A).
0.96 Rag2 promoter contacts and a reduction in ASE-Rag1 promoter contacts that fell just short of statistical significance (P = 0.06; Fig. 7 C).
0.96 Rag1 and Rag2 promoters (Fig. 8 C).
0.96 Rag1 promoter caused reductions in Rag2 expression that were comparable to the reductions in Rag1 gene expression.
0.96 Rag2 gene expression in Rag1 promoter mutants is likely secondary to the disruption of locus organization since in these mutants, the Rag2 promoter lost contact with both the Rag1 promoter and the ASE.
0.95 Rag1 promoter E2A and Runx sites are required for maximal endogenous Rag1 and Rag2 expression
0.94 Rag1 and Rag2 promoter mutations on transcription from the reciprocal promoter (Fig. 4 C).
0.94 Rag2 promoter contacts with both the ASE and the Rag1 promoter were disrupted in the absence of SATB1, even though ASE-Rag1 promoter interactions were maintained.
0.93 Rag1 and Rag2 expression (Fig. 7 D).
0.92 Rag2 promoter activity requires an intact and functional Rag1 promoter, whereas Rag1 promoter activity does not similarly require the Rag2 promoter; rather, an intact Rag2 promoter appears to diminish Rag1 promoter activity, suggesting the possibility of competition between the two promoters.
0.90 Rag1 and Rag2 promoters (Fig. 4 F) remains uncertain because Rag2 promoter deletion did not cause a significant increase in Rag1 promoter-ASE interactions (Fig. 6 E, left) or Rag1 promoter histone H3 acetylation (Fig. S3).
0.90 Rag2 promoter interactions, although contacts between the ASE and the Rag1 promoter were not obviously perturbed (Fig. 7 F).
0.85 Rag1 promoter binding sites for E2A or Runx1 also resulted in reduced contact frequencies between the ASE and the Rag1 and Rag2 promoters (Fig. 6 C, left) and between the Rag1 and Rag2 promoters (Fig. 6 C, right).
0.84 Rag1 promoter displayed substantial reductions in Rag2 gene expression; those with E2A site mutation trended similarly (Fig. 4 E, right).
0.84 Rag1 and Rag2 promoters (Fig. 6 B, left) and also between the Rag1 and Rag2 promoters (Fig. 6 B, right).
0.83 Rag1 promoter-driven reporter was expressed in both lymphoid and nonlymphoid cells, whereas a Rag2 promoter-driven reporter was active only in lymphoid cell lines.
0.83 Rag1 and Rag2 promoters in assays using the ASE as a viewpoint (Fig. 6, A and B, left) and frequent interactions between the Rag1 and Rag2 promoters in assays using the Rag1 promoter as a viewpoint (Fig. 6 B, right).
0.77 Rag2 promoter deletion, Rag2 lost contact with the ASE and Rag1 promoter, but Rag1 promoter-ASE interactions remained intact (Fig. 6 E).
0.76 Rag1 and Rag2 gene expression, we measured the effects of binding site mutations and transcription factor KOs on RAG locus conformation by performing chromosome conformation capture (3C) in VL3-3M2 cell clones.
0.68 Rag1 and Rag2 genes are convergently oriented, with their promoters separated by only ~25 kb.
0.66 Rag2 promoter did not reciprocally impair Rag1 gene expression.
0.57 Rag1 promoter integrity is as important as ASE integrity for the detected pairwise interactions among the ASE and Rag1 and Rag2 promoters.
20398922 0.98 RAG1 binding was detected only at regions containing recombination signal sequences, RAG2 binds at thousands of sites in the genome containing histone 3 trimethylated at lysine 4.
0.98 RAG1 and RAG2 to antigen receptor loci remains unknown.
0.98 RAG2 binding to H3K4me3 increases the catalytic activity of the RAG complex and hence might enhance this risk, as might the recently described interaction of RAG1 with histone H3.
0.98 RAG1 and RAG2 are co-expressed.
0.98 RAG2 is highly unstable in the S, G2, and M phases of the cell cycle and hence developing lymphocytes have periods during which RAG1 is present in the absence of RAG2.
0.97 RAG1/RAG2/HMGB1/2 first bind to one RSS and then capture a second RSS lacking bound RAG proteins to form the synaptic or paired complex (Fig. 1A).
0.97 RAG1 and RAG2 binding is greatly upregulated at Jkappa gene segments in pre-B cells as compared to pro-B cells (compare Figs. 1D, E with 2A, B), as is H3K4me3 (Fig. 2C), H3 acetylation, and association with RNAP II (data not shown).
0.97 RAG2 facilitates RAG1 recruitment/retention at Igh.
0.97 RAG1 and RAG2 efficiently associate with the J/proximal D regions of the Igh and Tcrbeta loci in pre-B/pre-T cells.
0.97 RAG2 need not exist in a stable complex with RAG1 and that developing lymphocytes contain a substantial pool of chromatin-associated RAG2 that is not in complex with RAG1.
0.97 RAG1 binding is more restricted than that of RAG2, being detected only in regions that display the two hallmark features of recombination centers: i) highly active chromatin and ii) the presence of arrays of RSSs.
0.97 RAG1 does not require RAG2 for binding and it is likely that direct interactions with the RSS play a critical role in RAG1 recruitment to recombination centers.
0.97 RAG2 to H3K4me3 followed by recruitment of RAG1; ii) binding of RAG1 to the RSS followed by recruitment of RAG2; and iii) binding of a pre-formed RAG1-RAG2 complex to the RSS and/or H3K4me3.
0.97 RAG1 binding to Igh, unlike the other antigen receptor loci examined, is dependent on the presence of RAG2 (Figs. 2A and S5A).
0.97 RAG2 to pINV-0 in the D345 cell line (Fig. 5D) represents a situation in which the RSS (presumably together with RAG1) facilitates RAG2 recruitment.
0.97 RAG2 levels rise at the beginning of G1, RAG1 is already localized to recombination centers and facilitates the recruitment of RAG2 (pathway ii above).
0.96 RAG1 and RAG2, probably together with high mobility group protein HMGB1 or HMGB2, bind to recombination signal sequences (RSSs) that flank V, D, and J gene segments (Fig. 1A).
0.96 Rag1-/- x B1-8i (R1-/- H) and Rag1-/- x 2B4 (R1-/- beta) mice (Fig. S1B, D), and express D708A RAG1 and RAG2 protein in thymocytes and bone marrow B lineage cells (Fig. S2A, B).
0.96 RAG1 and RAG2 to the recombination substrate under these assay conditions.
0.96 RAG1 to bind the RSS in the absence of RAG2 is consistent with the hypothesis that RAG1 evolved from the transposase gene of Transib transposons, which contain terminal inverted repeats resembling RSSs but no RAG2 homologue.
0.95 RAG1 and RAG2 to recombination signal sequences flanking antigen receptor V, D, and J gene segments, has not previously been characterized in vivo.
0.95 RAG2 binds very broadly in the genome at sites with substantial levels of H3K4me3, while RAG1 binding is more tightly restricted and likely requires direct interaction with the RSS.
0.95 RAG2 by itself would pose no threat to genome integrity, even inefficient recruitment of RAG1 to non-antigen receptor loci by H3K4me3-bound RAG2 would create a risk of aberrant DNA nicks or double strand breaks, particularly at nearby cryptic RSSs, non-B form DNA structures, or DNA mismatches (such as might be created by the activation induced deaminase).
0.95 RAG1 and RAG2 interact with one another, it is plausible that each RAG protein can increase the efficiency and rapidity of binding of the other in ways that are not captured in our analyses of primary lymphocyte populations.
0.94 RAG1 and RAG2 to the 5' portion of the Jalpha cluster was observed, with the strongest association seen at the most 5' TRAJ gene segments analyzed (TRAJ61 and TRAJ58) (Fig. 3A, B).
0.94 RAG1 and RAG2 was detected at both D-Jbeta clusters, but not at TRBC1, TRBC2, or the three Vbeta gene segments assayed (Fig. 4A, B, pink bars).
0.94 RAG1 and its tight association with as yet unknown elements of the nucleus have made it difficult to determine the extent to which RAG1 and RAG2 exist in RAG1-RAG2 complexes in vivo.
0.94 RAG1, RAG2, the Vkappa and Jkappa RSSs, and probably HMGB1/2.
0.93 RAG1 and RAG2 binding was observed in a small domain encompassing the Jh elements and closely linked DQ52 gene segment, but could not be detected at Vh gene segments, a DSP2 gene segment, or the frequently recombined DFL16.1 gene segment (Fig. 2A, B).
0.93 Rag1 and Rag2 expression and efficient recombination of Tcrbeta.
0.90 RAG1 and RAG2, and yet cells expressing only RAG1 or only RAG2 largely recapitulate the binding patterns observed in cells expressing both RAG proteins.
0.89 RAG1 and RAG2 associate with a small region encompassing some or all of the J gene segments in the Igkappa and Tcralpha loci and J and J-proximal D gene segments in the Igh and Tcrbeta loci.
0.88 RAG1 and RAG2 to Antigen Receptor Loci
0.88 RAG1 and RAG2 do not bind detectably to Dbeta, Jbeta, or Jalpha gene segments in WT pre-B cells, or to Vkappa or Jkappa gene segments in WT pre-T cells, while there appears to be a low level of binding in the vicinity of Jh1 in pre-T cells (Fig. S3D, E).
0.87 RAG1 and RAG2 to DNA
0.85 RAG1 protein that interacts with RAG2 and binds DNA normally but lacks catalytic activity.
0.76 RAG1 and RAG2 was detected to pINV-12/23 than to pINV-0 (Fig. 5C, D).
27436288 0.98 RAG1 binding patterns cannot be fully explained by co-recruitment to H3K4me3 through RAG2, and that RAG2-independent mechanisms contribute to the targeting of RAG1 to chromatin.
0.98 RAG2-independent recruitment mechanism is the direct interaction of RAG1 with histones (Figure 1A).
0.98 RAG1 ChIP-seq dataset from WT thymocytes, along with the published data described above, to show that factors distinct from H3K4me3 and RAG2 contribute to the chromatin targeting pattern of RAG1.
0.98 RAG2 and RAG1 (Figure 2A; Jalpha and Jkappa).
0.98 RAG1 binding and DNaseI-HS strengthened in both cR1 and R2DeltaC compared to WT (Figure 5C, bottom row and Supplementary Table S3), suggesting that the absence of either of the two presumed chromatin 'anchor' domains for RAG1 (the RAG2 PHD and RAG1 N-terminal region) allows for increased non-specific DNA binding.
0.98 RAG1 binding patterns are driven by RAG2-H3K4me3 dependent and -independent interactions, mediated, at least partially, by the RAG2-PHD and the non-core domain of RAG1, respectively (see Figure 5A for schematic representation).
0.98 RAG1 and RAG2 to bRSSs occurs both in vivo and in vitro.
0.98 RAG1-chromatin interaction is mediated by RAG2, which essentially acts as an adaptor to direct RAG1 to H3K4me3.
0.98 RAG2 C-terminus, specifically the PHD finger, in regulating both RAG1 binding and activity.
0.97 RAG1/RAG2 endonuclease initiates V(D)J recombination at antigen receptor loci but also binds to thousands of places outside of these loci.
0.97 RAG1 and RAG2 have been defined as the minimal portions required for RAG activity in vitro.
0.97 RAG1 binding patterns could reflect at least four distinct modes of substrate recognition (Figure 1A): (i) indirect recruitment via RAG2 to H3K4me3-rich chromatin, (ii) direct binding of RAG1 to histones, (iii) sequence-specific binding to RSSs or RSS-like sequences and (iv) non-specific binding to DNA.
0.97 RAG1 binding spreads to additional sites in the genomes of R2-/- and R2DeltaC thymocytes relative to thymocytes expressing WT RAG2.
0.97 RAG1 is thought to bind initially, the combination of high H3K4me3 levels and strong RSSs allows RAG2-bound RAG1 to interact with the RSSs.
0.97 RAG2 C-terminus decouples the indirect link between RAG1 and H3K4me3, selectively depletes RAG1 binding in the H3K4me3-driven Cluster 1 (Figure 5A) and allows for expanded RAG1 binding at thousands of new sites characterized by lower H3K4me3 density.
0.97 RAG1 binding sites reflects a RAG2-independent mode of interaction that depends, at least partially, on the non-core regions of RAG1, as manifested by depletion of RAG1 in the H3K27Ac-driven cluster of peaks in the absence of the non-core RAG1 regions.
0.96 RAG1 binding is driven by two distinct modes of interaction with chromatin: the first is driven by H3K4me3, promoter-focused and dependent on the RAG2 PHD, and the second is defined by H3K27Ac, enhancer-focused and dependent on 'non-core' portions of RAG1.
0.96 RAG1) and an essential cofactor (RAG2).
0.96 RAG1 and RAG2 binding patterns overlap with sites marked by H3K4me3.
0.96 RAG1 would depend strongly on its interaction with RAG2 and the ability of RAG2 to bind H3K4me3 via its PHD finger.
0.96 RAG1 binding in R2DeltaC thymocytes re-distributed toward Cluster 2 (H3K27Ac-driven) at the expense of Cluster 1 (H3K4me3-driven; P < 1e-8), consistent with the hypothesis that RAG1 binding to Cluster 1 is strongly dependent on RAG2-PHD interactions with H3K4me3.
0.96 RAG1 or the RAG2-PHD finger (Figure 5C).
0.95 RAG1 was found to occupy a subset of the RAG2(+) H3K4me3(+) sites in the genome.
0.94 RAG1 binding that are defined primarily by the histone marks H3K4me3 and H3K27Ac, and are dependent on the non-core regions of RAG2 and RAG1, respectively, with specific DNA binding making little contribution.
0.91 RAG2-independent modes of RAG1-chromatin interactions to become dominant, as discussed below.
0.89 RAG1 ChIP-seq data from R2-/- and R2DeltaC thymocytes in which the absence of RAG2 or its PHD finger removes the potential for indirect coupling of RAG1 to H3K4me3 via RAG2.
0.80 RAG1 binding pattern arises from a mixture of RAG2/H3K4me3-dependent and -independent modes, with the former decoupled in the absence of the RAG2 PHD finger and the latter decoupled in the absence of the RAG1 non-core regions.
0.71 RAG1 binding levels, however, are significantly lower in the total absence of RAG2 compared to both WT and R2DeltaC (Supplementary Figure S3C; Paired Wilcoxon test; P = 0).
0.62 RAG2-dependent and RAG1-intrinsic mechanisms in determining RAG1 binding patterns is not known.
0.58 RAG1 recruitment predominates in the absence of the RAG2 PHD, such that the RAG1 binding pattern shifts away from H3K4me3 and toward H3K27Ac.
0.55 RAG1 distribution, the RAG2 core region strengthens the overall RAG1 ChIP-seq signal (by an as yet unknown mechanism) but has little influence on RAG1 distribution (Supplementary Figure S3D).
27973733 0.98 RAG1 and RAG2.
0.97 RAG1 and RAG2 have been identified, but only recently has their function begun to be characterized, revealing mechanistic links to the vertebrate RAGs.
0.97 RAG1/RAG2 heterotetramer together with the high mobility group protein B1 or B2 (HMGB1 or HMGB2) to one RSS and synapsis with a partner RSS allows for the DNA cleavage reaction to proceed (Fig. 1b, c).
0.97 RAG2 (amino acids 1 to 352 in the mouse protein) (Fig. 2A) is made up of a single domain consisting of a six bladed beta propeller that interacts with RAG1 and with the coding segment DNA that flanks the heptamer of the RSS.
0.97 RAG1/RAG2 transposase genes from another site in the genome (perhaps a distinct integration of the RAG transposon) would have provided the necessary enzyme in trans to bind the TIRs and generate the DNA double stranded breaks needed to recreate a functional receptor gene.
0.97 RAG1 and RAG2.
0.97 RAG1 and Transib: both proteins have the capacity to function in the absence of RAG2, and yet both also have the capacity to interact physically and functionally with RAG2.
0.97 RAG1 and the ability of Hztransib transposase to mediate recombination when paired with mouse RAG2 provides evidence for a relationship between these proteins.
0.96 RAG2, providing the first functional link between these proposed ancient relatives and vertebrate RAG1.
0.95 RAG1-like and RAG2-like genes and flanked by TIRs that resembled RSSs (hereafter referred to as the RAG transposon), gave rise to the gene segments of the antigen receptor loci and to RAG1 and RAG2.
0.95 RAG2 to alter the biochemical activity of Hztransib transposase and lead us to suggest that collaboration between a RAG2-like protein and an early RAG1-like Transib would have led to enhanced transposition activity and perhaps altered TIR substrate preferences, with implications for how to integrate the various RAG-like proteins into the evolutionary history of the vertebrate RAGs (see model below).
0.95 RAG2 specifically facilitates Hztransib-mediated transposition with 23RSS but not 12RSS substrates, despite the fact that Hztransib does not contain a domain with detectable sequence similarity to the NBD of RAG1.
0.94 RAG1 is able to mediate V(D)J recombination in the absence of RAG2 have been confirmed, implying independent evolutionary origins for the two RAG genes.
0.94 RAG1/RAG2 proteins encoded either by the inserted TE itself or another copy of the TE present elsewhere in the genome.
0.93 RAG1, that RAG1 has low levels of V(D)J recombination activity in the absence of RAG2, a result also obtained in RAG2-deficient mice.
0.92 RAG1 and RAG2 being found adjacent to one other and convergently transcribed (Fig. 3A) in all jawed vertebrate genomes characterized to date, with an intergenic distance that is typically less than 10 kb.
0.91 RAG1 and RAG2 and the proteins they encode, and argues against an alternative proposal of a viral origin for RAG1.
0.89 RAG1-like gene (Fig. 3) leaving the origins of RAG2 uncertain and hinting at independent origins for the two RAG genes.
0.87 RAG1/RAG2 and a 12/23RSS pair remain to be determined.
0.84 RAG2 strengthens adherence to the 12/23 rule on the part of RAG1 argues that acquisition of a RAG2-like gene during formation of the RAG transposon could have strengthened or enabled a preference for asymmetry.
0.80 RAG1 and RAG2.
0.79 RAG1 core, the resulting chimeric protein was capable of mediating V(D)J recombination when paired with mouse RAG2.
0.79 RAG1 and RAG2 core regions, respectively, and have the potential to fold into tertiary structures similar to those adopted by the RAG cores (M. Surleac and A. Petrescu, personal communication).
0.71 RAG1/RAG2 along with HMGB1/2 (green oval) to a single RSS (triangle) (a).
0.51 RAG2 that is not already linked to a RAG1-like gene.
26234156 0.98 RAG1 endonuclease, together with its cofactor RAG2, is essential for V(D)J recombination but is a potent threat to genome stability.
0.98 RAG2, in contrast, is an accessory factor that enables RAG1 cleavage activity and enhances sequence-specific recognition of the RSS by RAG1.
0.98 RAG1 co-localized with a subset of RAG2 and H3K4me3 peaks (Figures 2A, 2D, and 2F; and Table S1), affixing a potent endonuclease to ~3,500 sites in the thymocyte genome.
0.98 RAG1 binding was reduced in magnitude and perturbed in thymocytes lacking RAG2 (Figures S1D, S2A, S3A, S3B).
0.97 RAG1 and RAG2, form an endonuclease with a preferred DNA substrate - the recombination signal sequence (RSS) - that immediately flanks V, D, and J gene segments.
0.97 RAG2 occupies a significant proportion of the active chromatin landscape, and that cRSSs are strewn about the genome, one might expect that the site-specificity of V(D)J recombination would be enforced through restriction of RAG1 binding to antigen receptor genes.
0.97 RAG1 is not exclusively targeted to the Ig and Tcr genes but instead colocalizes with RAG2 at thousands of sites.
0.97 RAG1, RAG2, and H3K4me3 spread into 3' Jalpha segments (Figure 1B: ii, v, viii).
0.97 RAG1 and RAG2 occurs in regions of the genome that are relatively depleted of potential cleavage sites.
0.97 RAG1 binding observed when RAG2 is absent or truncated suggest that the RAG1-RAG2 interaction is also a significant factor in localizing RAG1 to active chromatin.
0.96 RAG1 and RAG2 to open transcriptional regulatory regions might be relevant.
0.94 RAG1 and RAG2, perhaps as components of a transposable element, and their adaptation into the recombinase underlying adaptive immunity, presented a significant evolutionary challenge to vertebrate genome integrity.
0.94 RAG1 and RAG2 bind to thousands of sites in the lymphocyte genome
0.93 RAG1 and RAG2 with chromatin.
0.90 RAG2, binding is independent of RAG1, correlates tightly with H3K4me3, and appears to be strongly dependent on the RAG2 C-terminal region, in which the critical domain is almost certainly the PHD.
0.88 RAG1 binding density in pre-B cells), which features substantial RAG1 and RAG2 recruitment in both v-abl cell lines and primary pre-B cells (Figure 6B).
0.87 RAG1 and RAG2 ChIP-seq in their respective knock-outs; one exception is noted in Figure S2F) (Figures 1B and 2A: iii, vi) provided strong support for the veracity of these RAG1 binding sites.
0.87 RAG1/RAG2 binding.
0.86 RAG1, RAG2, and H3K4me3 over the 5' Jalpha segments (Figure 1A and 1B: i, iv, vii), the Dbeta1-Jbeta1 segments (Figure S1A), and Dbeta2-Jbeta2 segments (not shown), consistent with our previous analysis.
0.64 RAG2 binding patterns are RAG1-independent (Figures S1D: vi, vii; S2A: vi, vii), but require the RAG2 C-terminal region containing the PHD (Figures S1D: x; S2A: x).
24037181 0.98 RAG1 and RAG2 expression, proteins necessary for the expression of TCR, leading to TCR revision.
0.98 RAG1 and RAG2 translocate to the nucleus and induce rearrangements of the V, D and J regions of the TCR beta genes then V and J of the TCR alpha genes .
0.98 RAG1 and RAG2 resulting in BCR revision .
0.98 RAG1 and RAG2 (Fig. 1A).
0.97 RAG1 and RAG2 as well as with Ku-70 and translocates to the nucleus in Th40 cells.
0.97 RAG1 and RAG2 early in thymic T cell development.
0.97 RAG1 and RAG2 leading to altered TCR expression, assigning yet another role to this versatile molecule.
0.96 RAG1 coimmunoprecipitated RAG2 and Ku70 (Fig.1B).
0.95 RAG1 and RAG2 expression is attenuated by Fas in autoimmune derived Th40 cells
0.95 RAG1 and RAG2 in peripheral Th40 cells but it is interesting that it interacts with RAG1 in the nucleus while interacting with RAG2 only in the cytoplasm.
0.94 RAG1 and RAG2 protein expression by CD40 stimulation of NOD splenic, total T cells as well as of diabetogenic T cell clones .
0.93 RAG1 and RAG2 in autoaggressive T cells and Fas prevents CD40 induced RAG expression
0.92 RAG1 and RAG2 as well.
0.84 RAG1 and RAG2 as well as nuclear translocation of CD40 itself.
0.81 RAG1 but not RAG2 and stronger association with Ku80 than with Ku70 is intriguing.
0.80 RAG1, RAG2 and Ku-70
0.75 RAG1 and RAG2 protein expression in the CD40 stimulated sorted Th40 cells and determined whether Fas could affect CD40 induced RAG expression.
0.57 RAG1 and RAG2 in peripheral Th40 cells, we determined whether a similar association could be found in thymocytes.
21115692 0.98 recombination-activating gene 1 (RAG1) and RAG2 proteins to their DNA targets.
0.98 RAG2 is an essential cofactor for DNA cleavage via its interaction with RAG1, enhances RSS binding, and contributes important regulatory functions, such as binding to the N-terminal tail of histone H3 when lysine 4 is trimethylated (H3K4me3).
0.98 RAG1 and RAG2 bind to a focal region (termed the "recombination center") containing some or all of the J gene segments within the Ig heavy chain (Igh), Igkappa, Tcrb, and Tcra loci.
0.97 RAG1 binding globally at Jalpha or Dbeta/Jbeta gene segments, that promoters and transcription direct RAG1 binding locally, and that RAG1 binding can be targeted in the absence of RAG2.
0.97 RAG2 binding closely mirrored the distribution of H3K4me3 throughout the entire genome, RAG1 binding was suggested to be strongly dependent on direct recognition of the RSS.
0.97 RAG1 robustly and exhibits substantial H3 acetylation in Rag2-/- x Tcrb-transgenic thymocytes ( and not depicted).
0.97 RAG1 occurs in the presence or absence of RAG2.
0.96 RAG1 and RAG2, probably assisted by the high mobility group protein HMGB1 or HMGB2, bind one RSS and then capture a second RSS to create a synaptic complex.
0.96 RAG1 and RAG2 were found to be recruited independently of one another into Igkappa, Tcrb, and Tcra recombination centers.
0.95 RAG1/RAG2) access to the appropriate DNA substrates (RSSs) so that binding can take place.
0.91 RAG2, it is remarkable that RAG1 binding in the absence of RAG2 reflects so accurately the recombination defects of the mutant alleles.
0.89 RAG2 binding, as we have shown is the case for RAG1 binding (Fig. 2 B and Fig. 4 B).
0.86 RAG1 in the presence of HMGB1 (which was included to more closely mimic the conditions found in RAG2-deficient cells; Fig. S1).
0.85 RAG2 binding) are similar to those we observe for RAG1, and clearly depend on transcription.
0.72 RAG2 binding in our experiments, we expect that the pattern of RAG2 binding would closely resemble that of RAG1 in these mutant Tcra and Tcrb alleles, for two reasons.
0.66 RAG1 and RAG2 binding patterns in antigen receptor loci.
14624253 0.98 RAG-1 and RAG-2, is repressed by constitutive signals requiring the adapter molecules LAT and SLP-76.
0.98 Rag-1 and Rag-2 as Rag) expression is strictly regulated, allowing sequential rearrangements of the TCRbeta and TCRalpha genes.
0.98 RAG-1 and RAG-2, expressed at higher levels than wild-type Jurkat (left three columns in red in Figure 1B).
0.98 RAG-1 and RAG-2 particularly interested us since it has been well established that induction of the TCR signaling pathway is able to terminate Rag gene expression.
0.98 Rag-1 and Rag-2 are expressed in DP thymocytes and turned off during subsequent thymic maturation.
0.98 RAG-1 and RAG-2 to a level similar to that in J.CaM2 cells, suggesting that basal Lck and/or Fyn kinase activity is required for constitutive repression of these genes (Figure 3Ch).
0.98 RAG-1 and RAG-2 expression in Jurkat cells (for a model, see Figure 8).
0.98 Rag-1 and Rag-2.
0.97 Rag-1 or Rag-2 are arrested at the same stage, thus linking the genes responsible for recombination and subsequent expression of the TCR with the downstream signaling pathways.
0.96 RAG-1 and RAG-2 Relies on a Signaling Competent LAT Molecule
0.95 Rag-1 and Rag-2 are unusual genes in that they have remained linked and conserved throughout evolution, are orientated in opposite directions, and are exclusively coexpressed in lymphoid cells (, 1992).
0.94 Rag-2 essential for normal expression of both Rag-1 and Rag-2, whereas DP cells needed an 110 kb region upstream of Rag-2 for both genes.
0.93 RAG-1 and RAG-2 Requires a Signaling-Competent LAT Molecule
0.80 RAG-1 and RAG-2, we plotted the expression profiles of genes whose expression was elevated in J.CaM2 relative to Jurkat cells and diminished by restoration of LAT function in J.CaM2-LAT (Figure 3D).
0.74 Rag-1 and Rag-2 loci were mapped in studies of transgenic mice carrying bacterial artificial chromosomes encompassing different portions of the Rag locus.
29755449 0.98 RAG1 and RAG2 enzymes.
0.98 Rag1 and Rag2 is tightly controlled and occurs primarily during the early developmental stages of T and B cells.
0.98 Rag1 and Rag2.
0.97 Rag1, Rag2, Aicda, or Ung genes was observed in either alum-injected or alum + KLH-immunized group (Table 2), indicating that DRG sensory neurons lack the genetic make-up to produce antibodies.
0.97 Rag1 and Rag2 transcripts in DRG sensory neurons harvested from immunized mice.
0.96 RAG1, RAG2, AID, or UNG) required for generating antibody diversity and, therefore, cannot make antibodies.
0.96 Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO) or muMT mice].
0.95 Rag1 and Rag2 are differentially expressed in immunized mice.
0.94 Rag1 and Rag2 transcripts have been reported in a variety of non-lymphoid cells, including different cancer cell types, epithelial cells and neurons, to our knowledge, no functional role for these enzymes have been identified in non-lymphoid cells.
0.94 RAG1 or RAG2 enzymes lack mature lymphocytes and fail to generate antibodies due to their inability to initiate V(D)J rearrangement.
0.91 Rag2 but no Rag1 transcripts present in DRG sensory neurons.
0.86 Rag1, Rag2, Aicda, and Ung transcripts.
0.80 Rag1, Rag2, Aicda, or Ung genes.
0.58 Rag1, Rag2, Aicda, and Ung were observed in the naive spleen.
0.58 Rag1, Rag2, or Aicda expression.
27825771 0.98 RAG1 and RAG2 genes, as well as previous findings that purified core RAG proteins can indeed complete the transposition reaction by catalyzing strand transfer of RSS signal ends into target DNA.
0.98 RAG1 and RAG2 regulate V(D)J recombination by affecting cell cycle-dependent degradation, cellular localization, and the stability of RSS-RSS complexes during the course of the reaction.
0.97 RAG1 and RAG2, guides the initial DNA cleavage events to the recombination signal sequence (RSS), which flanks each gene segment.
0.97 RAG1 and RAG2, initiate V(D)J recombination by generating DNA double strand breaks (DSBs) at the border of the gene segment and flanking RSS through a two step nicking and hairpin formation mechanism.
0.97 RAG1 and RAG2 proteins form a complex in the absence of DNA, and bind the RSSs as a single heterotetrameric complex that consists of two subunits each of RAG1 and RAG2, referred to as the RAG12RAG22 complex (Figure 1B).
0.96 RAG2 is less clear, but may function to activate RAG1 for sequence-specific binding and cleavage, and also provide additional DNA binding capability.
0.96 RAG1, residues 537-553 and 750-782, were shown in biochemical studies to be important in complex formation with core RAG2.
0.96 RAG2 mediate the majority of interactions with RAG1 (Figure 3).
0.95 RAG1 C-terminal domain that includes residues 827-835 in mouse RAG1 interacts with the RAG2 subunit from the opposite 'Y' branch by forming contacts with residues 308-314 (located on the intervening loop between propeller blades 5 and 6).
0.94 RAG1 and RAG2 core regions obtained from crystallography and cryo-electron microscopy (cryo-EM) studies have provided much anticipated views into the catalytically active V(D)J recombinase complex.
0.94 RAG2 on the conformation of core RAG1, and do these structural changes activate RAG1 for DNA cleavage activity?
0.93 RAG2 affecting the conformation of RAG1 and/or suppressing its nonspecific DNA binding ability.
0.81 RAG2 does not directly contact the heptamer, although its presence has previously been shown to increase the specific interaction of RAG1 for the heptamer.
0.63 RAG1 and RAG2: Domain architecture, complex interface, metal binding, and RSS interactions
27880903 0.98 RAG1 and RAG2 expression and continuous light chain editing.
0.98 RAG1 and RAG2, both normally expressed in pro-B and pre-B cells, with no detectable transcription in peripheral B cells.
0.98 RAG1 and RAG2.
0.98 Rag1 and Rag2 were expressed in Dicer- Drosha-, and DGCR8-deficient EmuBcl2 rescued Iglow cells suggesting that miRNAs regulate Rag1 and Rag2 mRNA expression.
0.98 Rag1 and Rag2 during light chain rearrangement and receptor editing in pre-B and immature B cells have been shown to be regulated by forkhead box O (FOXO)1 downstream of the PI3K/AKT pathway.
0.98 Rag1 and Rag2 indicated ongoing IgL gene rearrangement in peripheral B lymphocytes in the absence of miRNAs.
0.98 Rag1 and Rag2 during light chain rearrangement in pre-B cells and light chain editing in immature B cells lacking a functional light chain, expressing an auto-reactive BCR or having insufficient BCR "tonic" signal.
0.97 Rag1 and Rag2 mRNAs harbors very few putative target sites for miRNAs, and the few predicted sites that are revealed by Targetscan and PicTar algorithms are complementary to miRNAs that are not thought to be expressed in B lymphocytes.
0.96 Rag1 and Rag2 mRNA was readily detectable, consistent with ongoing Ig light chain rearrangement.
0.95 Rag1 and Rag2 expression after 5 hr incubation and became more notable at 24 hr.
0.95 Rag1 and Rag2.
0.83 Rag1 and Rag2 mRNAs are not likely to be direct targets of miRNAs.
0.65 Rag1 and Rag2 expression, albeit to a lesser extent.
0.58 Rag1 and Rag2 at levels similar to non-treated mice (Figure S6B).
23110142 0.98 Rag1, Rag2, and D-to-J rearrangement of the immunoglobulin (Ig) heavy chain locus.
0.98 Rag1 and Rag2 proteins are expressed in early stages of B cells to regulate V(D)J rearrangement of the Ig heavy and light chain loci.
0.98 Rag1 was expressed equally in pDCs and B cells, the expression of Rag2 was 3-fold higher in pDCs than in B cells (p<.05), indicating that Rag2 is preferentially expressed in pDCs.
0.98 Rag2+/+) and Rag1-/- bone marrow cells produced a large amount of IFNalpha in response to CpG, the induction of IFNalpha was significantly lower in Rag2-/- bone marrow cells (Fig. 4A, left panel, p<.05; and Fig. S3), suggesting that Rag2 may be required for TLR9-mediated production of IFNalpha in the bone marrow.
0.98 Rag2 couples with Rag1 to regulate V(D)J recombination.
0.98 Rag2 is generally thought to function by pairing with Rag1, recent evidence has shown that only Rag2 is essential for maintaining genomic stability since knockout of this protein, but not knockout of Rag1, on p53-/- background leads to rapid formation of thymic lymphomas.
0.96 Rag1 and Rag2 were highly expressed in pDCs and B cells but not in other cells (Fig. 2A ).
0.96 Rag1-/- pDCs, the increase of IRF8 was much lower in pDCs lacking Rag2 (Fig. 7A and Fig. S4).
0.94 Rag1 and Rag2 transcripts have been found in non-T/B cells such as dendritic cells and natural killer cells.
0.91 Rag1 and Rag2 expression in B cells, pDCs, and other cells in the mouse bone marrow.
0.85 Rag2-/- mice would differ in the expression of Rag1 and other B-lineage associated genes.
0.79 Rag2-/- bone marrow cells had a defect in CpG-mediated IFNalpha induction but Rag1-/- bone marrow cells did not (Fig. 4A, left panel and Fig. S3).
0.78 Rag2-/- pDCs expressed a high level of Ly6C but Rag1-/- pDCs expressed a similar amount of Ly6C as wildtype pDCs (Fig. 3C and Fig. S2).
24653725 0.98 RAG1 and RAG2, necessary for V(D)J recombination, and activation-induced cytidine deaminase, an essential mutator protein for catalyzing class switch recombination and somatic hypermutation, are regulated by various ubiquitination events that affect protein stability and activity.
0.98 RAG1 and RAG2 respectively, are necessary and sufficient for the breaks and rearrangements during V(D)J recombination.
0.98 RAG1 and RAG2, collectively referred to as RAG in this review, are lymphoid-specific proteins that cleave and join DNA segments during V(D)J recombination [reviewed in Ref. ].
0.98 RAG1 with core or full-length RAG2 co-purifies with a complex containing VprBP, DDB1, Cul4A, and Roc1 (VDCR complex) in vitro, which is known to act as a recruitment scaffold for repair proteins (Figure 1E).
0.98 RAG2, like RAG1, has a defined core region (amino acids 1-383) located at the N-terminal end and with core RAG1, is required for V(D)J recombination [reviewed in Ref. ].
0.98 RAG2 core is known to be critical for DNA cleavage and enhances DNA binding and specificity of the RAG complex, probably through its interaction with RAG1, as RAG2 itself has little or no DNA-binding activity.
0.98 RAG2 together with RAG1 is required for catalysis of V(D)J recombination events, its nuclear retention during G1 is important.
0.98 RAG2, RAG1 can remain bound to DNA where its RING E3-ubiquitin ligase activity can ubiquitinate histone H3 and/or VprBP, as discussed earlier.
0.96 RAG1 and RAG2, to rearrange multiple gene segments and select a V(D)J exon in the immunoglobulin heavy chain (IgH) and a VJ exon in the immunoglobulin light chain (IgL) loci.
0.96 RAG1 and RAG2 is crucial both for efficient V(D)J recombination to generate the diversity in the adaptive immune system and for avoidance of genomic instability.
0.96 RAG1 and RAG2 activity and protein stabilization, as well as a range of alternative downstream pathways, have tentatively been identified.
0.96 RAG1 is catalytically compromised in the absence of RAG2 for V(D)J recombination activity, it still retains its E3-ubiquitin ligase activity.
11514603 0.98 RAG1 and RAG2 expression in DP thymocytes.
0.98 RAG2 promoter is required for RAG1 and RAG2 expression in DP T cells 22.
0.97 RAG1 and RAG2 which recognize and cleave recombination signal sequences located adjacent to the coding V, D, and J segments 2 3 4 5.
0.97 RAG1 -/- and RAG2 -/- mice appeared to be reconstituted by the RYAC transgene as measured by the number of cells in the thymus and spleen.
0.95 RAG1 and RAG2 6 7 or factors that repair the double strand DNA breaks created during V(D)J recombination there is a complete block in the early stages of B and T cell development 8 9 10 11 12 13 14 15.
0.95 RAG1 and RAG2 expression in DN thymocytes in RYAC mice resembles that found in BAC transgenic mice and that this level of expression is sufficient for TCRbeta V(D)J recombination.
0.94 RAG1 and RAG2 expression in these mice is missing a distal regulatory element essential for reinduction.
0.93 RAG1 and RAG2 are closely linked genes that are believed to originate from a transposon which entered the vertebrate lineage at the time of the evolution of jawed fish 2 4 5 46 47 48 49 50 51 52 53.
0.93 RAG1 and RAG2 reinduction and also reconcile the apparent discrepancies between the two sets of in vivo experiments.
0.67 RAG1 and RAG2 expression in DP cells we analyzed T cell development in RYIIRAG1 -/-, RYIIRAG2 -/-, and RYIIIRAG1 -/- mice.
0.65 RAG1 or RAG2 expression in DP thymocytes in RYIIRAG1 -/-, RYIIIRAG1 -/-, and RYIIRAG2 -/- mice (60-120-fold less than in wild-type mice in five experiments).
25198102 0.98 RAG-1 and RAG-2 promoter activities in non-lymphoid cells owing to transcriptional interference caused by NWC transcription proceeding through RAG-2 promoter and RAG-1/RAG-2 cis-regulatory elements localized upstream RAG-2 gene.
0.98 RAG-1 and RAG-2 genes, which are tightly controlled throughout lymphocyte development.
0.98 RAG-1 promoter but not to RAG-2 promoter.
0.96 RAG-1 and RAG-2 locus encoding a protein complex indispensable for the recombination of immunoglobulin and T-cell receptor minigenes.
0.95 RAG-1 and RAG-2 genes raises additional questions concerning the nature of primordial RAG transposon.
0.89 RAG-1/RAG-2 genes has ignored, however, the existence of NWC gene, which most probably was the host gene for RAG transposon integration.
0.88 RAG-1 gene, a modified version of the hypothesis has been put forward, suggesting that only RAG-1 gene was a part of a mobile element which integrated within RAG-2 locus.
0.79 RAG-1-containing element integrated twice with RAG-2 locus this again argues for the "RAG-1 and RAG-2" hypothesis and suggests that the transposon independently infected the ancestors of jawed vertebrates and echinoderms.
0.69 RAG-1 and RAG-2 genes were found, the RAG and NWC loci are separate.
0.68 RAG-2 and the bidirectional activity of NWC promoter is typical for many host genes controlling transposon-related genes, it is reasonable to assume that the genetic element which integrated within NWC locus contained both RAG-1 and RAG-2 genes.
28532625 0.98 Rag1, Rag2, and Gadd54alpha transcripts and Rag1 and Gadd45a protein each decrease in an ATM-dependent manner after induction of RAG Igkappa DSBs.
0.98 Rag1 and Rag2 transcription in a single pre-B cell line.
0.98 Rag1 and Rag2 transcripts via mechanisms dependent on Nemo, consistent with a role for repression of Rag1 and Rag2 transcription by the p50 NFkappaB protein.
0.98 Rag1 and Rag2 transcripts concomitant with ATM-dependent loss of FOXO1 transcription factor binding to the Rag1/Rag2 locus Erag transcriptional enhancer.
0.98 Rag1 and Rag2 transcription (Figure 3).
0.98 Rag1 and Rag2 transcripts in pro-B and pro-T cells and ATM-deficiency increases bi-allelic V recombination and allelic inclusion for Igh and Tcrb loci.
0.98 Rag1 and Rag2.
0.97 RAG1/RAG2 (RAG) endonuclease initiates V(D)J recombination by introducing DNA double strand breaks (DSBs) adjacent to V, D, and J gene segments.
0.97 Rag1 and Rag2 transcription without affecting mechanisms by which ATM repairs DSBs.
0.95 Rag1 or Rag2 transcripts in pre-T cells, it will be important to determine whether DSBs repress RAG expression via lymphocyte developmental stage- and/or lineage- specific mechanisms.
32139788 0.98 RAG2 is a vital allosteric factor whose principal function seems to interact with RAG1 and activate the enzymatic activity of RAG1 endonuclease.
0.97 RAG1 and RAG2.
0.96 RAG1/RAG2 complex (RAG) within specific genomic recombination signal sequence (RSS) sites.
0.96 RAG2-deficient pro-B cell lines when zRAG2 was combined with mRAG1 than when mRAG2 was combined with the same mRAG1 (Fig. 1I,J).
0.95 RAG1 and RAG2.
0.91 RAG2 can alter the conformation of RAG1 and stabilize interactions of RAG1 with the heptamer.
0.87 RAG2 would lead to structural destabilization of the RAG2 protein or RAG1/2 complex.
0.73 RAG2, but not RAG1, contributed to the attenuated recombination efficiency.
0.65 RAG1 can be regarded as the activator whereas RAG2 can be referred to as the cofactor.
0.63 mRAG1/mRAG2 group regardless of whether the cells were co-transfected with coding joint (pCJGFP) or signal joint (pSJGFP) plasmids (Fig. 1A,B and Fig. S1A,B,E).
14581608 0.98 RAG1 and RAG2 are the lymphocyte-specific components of the V(D)J recombinase.
0.98 RAG1 and RAG2 are necessary in vivo and sufficient in vitro for initiation of V(D)J recombination (for review see reference).
0.97 RAG1 and RAG2 proteins via introduction of DNA double strand break (DSBs) between the V, D, and J coding segments and flanking recombination signal (RS) sequences.
0.97 RAG1- (and RAG2-) deficient mice exhibit a complete developmental block.
0.96 RAG1 (aa 384-1,008 of 1,040 residues) and core RAG2 (aa 1-383 of 527 residues) comprise the minimal regions of RAG1 and RAG2 necessary for recombination of extrachromosomal substrates in nonlymphoid cells.
0.95 RAG1 or RAG2 lead to a complete block in lymphocyte development in mice and are a cause of human T-B- SCID.
0.94 RAG1 or RAG2 that result in reduced, and possibly altered, V(D)J recombinase activity lead to Omenn Syndrome (OS), a disease characterized by lack of B cells and a reduced, oligoclonal T cell repertoire.
0.92 RAG1 are required for complete DH to JH rearrangement in A-MuLV transformants, whereas the COOH terminus of RAG2 may be more important for VH to DJ H rearrangement than for DH to JH rearrangement.
0.81 RAG1 and RAG2 proteins have been extensively characterized in vitro using purified proteins and defined DNA substrates (for review see reference).
21248269 0.98 RAG-1 and RAG-2 relative to nontransgenic littermates, presumably because of the feedback regulation that maintains allelic exclusion (Fig. 1 D, lanes Ig-Tg, and Table 2).
0.97 RAG-1 and RAG-2, and that the levels of RAG mRNAs are highest in cells that have bound (auto)antigen in the bone marrow.
0.97 RAG-1 and RAG-2 accompanied by increased lambda light chain gene rearrangement in the bone marrow of centrally deleting mice raises the question of feedback in hematopoiesis.
0.94 RAG-1 and RAG-2 levels that approached the levels in nontransgenic mice (Fig. 1 D, lanes Ig-Tg/H-2b and Ig-Tg/H-2k, and Table 2).
0.92 RAG-1 and RAG-2 mRNA in bone marrow cells of centrally deleting mice; (b) elevated expression of these recombinase genes in sIgM+ bone marrow cells of centrally deleting mice; (c) elevated levels of light chain rearrangement excision products in bone marrow cells of centrally deleting mice; and (d) expression of endogenously encoded light chain protein in cells expressing transgenic Ig in bone marrow cells of centrally deleting mice.
0.75 RAG-1 and RAG-2, but not TdT, in the bone marrow of centrally deleting mice detected using a PCR assay.
0.72 RAG-1 and RAG-2 levels.
0.56 RAG-1 and RAG-2 (Fig. 1 D, lanes Ig-Tg/H-2Kb periphery, and Table 2).
0.54 RAG-1 and RAG-2 in their bone marrow, but had no more bone marrow B cells than centrally deleting mice expressing the low affinity ligand Kb (Table 1).
22567371 0.98 RAG-1 and RAG-2 form a specific endonuclease in immature lymphoid cells.
0.98 RAG-1 and RAG-2 in immature lymphocytes explains the specificity of the V(D)J recombination process in these cells.
0.98 RAG-1 binding to accessible RSSs can be targeted in the absence of RAG-2, which is recruited directly to trimethylated H3K4 (H3K4me3), a mark of open and active chromatin.
0.98 RAG-2 protein and directly contributes to the opening of the chromatin by either repositioning or evicting nucleosomes, which allows free access of the RAG-1 protein to RSSs.
0.98 RAG-2 also recruits other chromatin remodeling complexes such as the ATPase RSC, ISWI, or SWI/SNF that can reposition or evict nucleosomes to facilitate the passage of the RNAPII that can be involved in recruitment of RAG-1.
0.98 RAG-2 through interactions with specific H3K4me3, whereas RAG-1 binds to accessible RSSs derived from transcriptional elongation in large loci.
0.96 RAG-1 and RAG-2 proteins induced germline transcription and V(D)J recombination at the Igk, Tcrg, and Tcrd loci; OcaB-/- mice displayed defective transcription and recombination of a subset of Vkappa gene segments; Stat5 is required for the transcription and VgammaJgamma recombination at the Tcrg locus in response to IL-7; and deletion of the enhancers and promoters at Tcr and Ig loci or inclusion of mutations at motifs for required transcription factors within these cis-elements inhibit both transcription and V(D)J recombination at each locus.
0.96 RAG-1 and RAG-2 proteins in the absence of ongoing transcription; however, the chromatin structure of the receptor antigen loci could remain accessible during nuclei isolation.
0.94 RAG-2 protein through H3K4me3 and recruitment of the RAG-1 protein to accessible RSSs.
23104096 0.98 RAG1 and RAG2, to loci destined for rearrangement.
0.98 RAG2 binds H3K4me3 leads to a model where epigenetic histone modifications mark a locus for RAG1-RAG2 recruitment.
0.98 RAG1-RAG2 recruitment.
0.96 RAG1-RAG2 introduce double-strand breaks at special recombination signal sequences (RSSs) that flank gene segments to initiate recombination.
0.94 RAG1 and RAG2 re-distribute towards the DJH junctions on rearranged alleles.
0.92 RAG1-RAG2 not only maximizes utilization of the DJH RSS for VH recombination, but also serves to limit the low but detectable occurrence of direct VH to JH rearrangements
0.88 RAG1 and RAG2 were highly enriched at a recombined DSP2.2 gene segment.
0.86 RAG1-RAG2 at DJH junctions and very little at germline DH gene segments.
0.66 RAG1-RAG2 binding is re-distributed towards the DJH junction on WT alleles and does not extend to the closest unrearranged DH gene segment.
19359154 0.98 RAG)1 and RAG2 are expressed in developing B and T lymphocytes and are required for the rearrangement of antigen receptor genes.
0.98 RAG1 and RAG2 are essential components of the enzyme complex that initiates assembly of antigen receptor genes from their component V, D, and J gene segments in both B and T cells.
0.98 RAG2 promoter that directs RAG expression in DP T cells and counteracts a silencer element found in between RAG1 and RAG2.
0.98 RAG1 and RAG2 are coordinately regulated by enhancer elements that seem restricted to the region 5' of RAG2.
0.97 RAG1 or RAG2 result in a complete and early block in both B and T lymphocyte development.
0.93 RAG1 promoter appears promiscuous while the RAG2 promoter shows a degree of lymphoid specificity.
0.87 RAG1/NWC hybrid and RAG2 transcripts result in the generation of siRNAs?
0.52 RAG1 and RAG2 are convergently transcribed, contain single large coding exons and are separated by only ~8kb.
19500590 0.98 RAG1 and RAG2, which together create a double-strand break between the RSS heptamer and the adjacent gene segment through a two-step mechanism.
0.98 RAG1 contains the active site and RSS binding sites, RAG2 is required for DNA cleavage activity.
0.96 RAG1/RAG2 complex can bind, but not cleave, RSS substrates in the presence of Ca2+.
0.96 RAG1-RAG2 V(D)J recombinase.
0.95 RAG1 contains the RSS heptamer and nonamer binding sites, and can bind to DNA in the absence of RAG2.
0.92 RAG2 may promote catalytic activity by forming additional contacts with the RSS or by indirectly enhancing recognition of the RSS by RAG1.
0.90 RAG1 and RAG2 are accomplished with these truncated proteins, which are the minimal catalytically active regions required for double-stranded DNA cleavage activity and also are more soluble than their full-length counterparts.
0.60 RAG1:RAG2:12-RSS complex for both the H937A and H942A mutants based on the diminished intensities of the supershifted bands (Figure 6A, lanes 3 and 5).
21354115 0.98 RAG1 and RAG2 mediate VDJ recombination, a process necessary for the maturation of B- and T-cells.
0.98 RAG1 but not RAG2 is expressed in the CNS, the only tissue outside of the immune system shown to express RAG.
0.98 RAG1 and RAG2, the RAG1 protein contains the catalytic DNA-binding core of the recombinase.
0.98 RAG2 with RAG1 have been observed in numerous proteins, and the discovery that a single kelch motif can mediate protein-protein interactions between RAG2 and RAG1 offers the possibility RAG1 may interact with as yet unidentified protein(s) in the CNS.
0.96 RAG1 and RAG2 enzymes, which together cleave Variable, Diversity, and Joining (VDJ) gene segments located on several chromosomes.
0.96 RAG2KO mice show exactly the same immunodeficient phenotype as RAG1KO, only RAG1 was shown to be expressed in the brain.
0.64 RAG1HET compared to RAG2HET could indicate effects of RAG1 hyposufficiency in the brain).
0.56 RAG1 and RAG2 null mice are both immunodeficient, the results suggest that the memory impairment is not an indirect effect of immunological dysfunction.
26301565 0.98 Rag1 and Rag2 and accessibility of targeted genes to the recombination machinery.
0.98 RAG1 and RAG2 are recruited to thousands of sites bearing H3K4me3.
0.98 RAG1 and RAG2 are recruited to thousands of genes most of which are accessible and bear the usual marks of open chromatin.
0.97 RAG1 and RAG2 binding at Jkappa that extended proximally to the kappaGT transcription start site (TSS) (Fig. 8b).
0.97 RAG1 and RAG2 recruitment were reduced approximately 4-fold in Brwd1mut small pre-B cells as compared to wild-type cells (Fig. 8d).
0.86 Rag1 and Rag2 expression were only slightly diminished in Brwd1mut small pre-B cells (Supplementary Fig. 7f).
0.85 RAG1 and RAG2 bind permissively across the genome with 2685 RAG1/RAG2/H3K4me3 co-incident peaks (Fig. 8a).
0.85 RAG1/RAG2/H3K4me3 at open chromatin (Fig. 8c) was very restricted with only 16 co-incident peaks occurring near 13 genes.
9670048 0.98 recombination activating gene (RAG)-1 and RAG-2.
0.98 recombination activating gene (RAG)-1 and RAG-2 during the early stages of B cell development in the bone marrow.
0.98 RAG-1 and RAG-2 proteins are reexpressed in germinal center (GC) B cells in secondary lymphoid tissues of immunized mice.
0.98 RAG-1 and RAG-2 proteins are expressed in GC B cells in popliteal LNs after immunization.
0.98 RAG-1 and RAG-2 proteins in GCs.
0.97 RAG-1 and RAG-2.
0.96 RAG-1 and RAG-2 in GC B cells.
20454452 0.98 RAG-1 and RAG-2 encode RAG-1 and RAG-2 proteins that together form a complex responsible for recognizing and cutting V, D and J segments thereby initiating V(D)J rearrangement.
0.96 RAG-1 and RAG-2 proteins are strictly required to ensure V(D)J recombination, and indicate that RAG-1 alone may be sufficient to induce, although at very low level, some TCR recombination.
0.91 RAG-2 (or RAG-1) deficient TCR Tg mice.
0.86 RAG-1- or RAG-2-deficient mice we have analyzed and which are currently in use are still able to perform V(D)J TCR recombination and that this process is independent of the specificity and site of insertion of the TCR Tg.
0.86 RAG-1 alone could perform VDJ recombination since it has both specific DNA binding domains and catalytic sites for DNA cleavage (in agreement, we revealed the presence of rare isolated mRNA transcripts showing TCR chain rearrangements in the spleen cells of a non-Tg RAG-2 deficient mouse), this hypothesis is very unlikely for RAG-2 since it lacks both DNA binding activity and catalytic activity.
0.54 RAG-1 and RAG-2 KO mice, a highly improbable event due to the physical linkage of the two loci).
0.53 RAG-1 or RAG-2-knocked out mice have no detectable T and B cells and when crossed into a TCR Tg background, they appeared to contain a single homogeneous monoclonal population of mature T-cells expressing the TCR-Tg and no B cells.
26104458 0.98 RAG1 and RAG2, which work together with non-lymphoid-specific DNA bending factors, HMG1A or HMG1B to carry out DNA cleavage.
0.98 RAG2, leading to the view that RAG1 is the catalytic component of the recombinase, with RAG2 serving as an essential cofactor with some regulatory activities (described below).
0.97 RAG1 and RAG2 transgenes under the control of strong promoters causing constitutive expression during lymphocyte development and in extra-lymphoid tissues results in a spectrum of phenotypes (including lymphopenia, growth retardation, and early death) reminiscent of DNA damage deficiency syndromes.
0.96 RAG1 and RAG2 is carefully limited in a cell- and developmental stage-specific fashion.
0.96 RAG1 or RAG2 which destabilize the complex allow the ends to be joined by alternative pathways, including homologous recombination and aNHEJ.
0.93 RAG1, RAG2, a divalent metal ion, and HMGB1 or HMGB2.
0.53 RAG1 and RAG2 genes are located quite close to each other in all species examined, and their ORFs are generally encoded in single exons.
29925675 0.98 RAG1-RAG2 endonuclease complex.
0.97 RAG1 and RAG2), which together comprise the site-specific endonuclease that introduces DNA double strand breaks at the recombination signal sequences (RSSs) flanking Ig gene segments.
0.95 RAG1 may provide a means to restrain V(D)J recombination during a phase of the cell cycle when RAG2 levels are fixed.
0.93 Rag1 and Rag2 transcript levels were only found to be elevated in sorted B cells from Dicerdel/delBcl2+ mice, and not VprBPdel/delBcl2+ mice, consistent with the block in Rag transcription observed in cultured BM cells from the latter mice (Fig. 2H).
0.93 Rag1 and Rag2 transcript were slightly diminished in both the VprBP- and Dicer-deficient BM cultures (Fig. 3C).
0.91 RAG1 levels, but not RAG2 levels, and promotes greater V(D)J rearrangement of the GFP reporter substrate in these cells is consistent with this possibility.
0.86 RAG2 is expressed in molar excess to RAG1 (~15-fold); therefore, one would expect the latter to be rate-limiting for V(D)J recombination.
14769852 0.98 RAG1 and RAG2 are tightly regulated: rag expression is limited to specific developmental subsets of B and T lymphocytes, and RAG2 protein must be resynthesized and relocalized to the nucleus with every cell cycle.
0.98 rag2 is sufficient for both complementing lymphocyte development in rag2 -/- animals and controlling normal expression of rag1 and rag2 in B and T lineage progenitors.
0.98 rag2 gene, profoundly influences expression of both rag1 and rag2 in a B lineage-specific manner.
0.96 rag1 and rag2 in B lineage progenitors leading to a partial block in B cell development, whereas T cell development remains unaffected.
0.94 rag2 transcripts and a 10-fold reduction in rag1 transcripts in pro- and pre-B cells, whereas the T lineage remains unaffected.
0.60 recombinase-activating gene (RAG)1 and RAG2 as well as the DNA repair proteins Ku70 and Ku80, DNA-PKcs, DNA ligase IV, XRCC4, and Artemis.
17273993 0.98 Rag1 and to a lesser extent Rag2 is down-regulated in adult DN4 cells relative to DN3 cells.
0.97 Rag1, Rag2 or TCRbetadelta-deficient mice is arrested at the DN3 stage leading to the assumption that pre-TCR signalling and beta-selection occur at, and are obligatory for, the transition from DN3 to DN4.
0.97 Rag1, Rag2 or TCRbetadelta is arrested at the DN3 stage.
0.97 Rag1 and Rag2 is down-regulated in the foetal DN4 population
0.95 Rag1-/- thymocytes were treated with antiCD3 antibody for 24 h to mimic the pre-TCR signal, down-regulation of Rag2 transcription was even greater (6-12-fold) compared to down-regulation of Rag2 in foetal DN4 wild-type thymocytes (Fig. 3B).
0.82 Rag1 and Rag2 genes in foetal and adult DN3 and DN4 thymocyte subsets and TCRbeta locus rearrangement.
19734904 0.98 RAG1 and RAG2 is sufficient to induce Igkappa recombination in a non-lymphoid cell line.
0.98 Rag1 and Rag2 (Fig. 3a and 3b) and enhanced Igkappa germline transcription (Fig. 3c).
0.97 Rag1, Rag2 (Fig. 1c) and Igkappa germline (Fig. 1d) was induced upon IL-7 withdrawal.
0.96 Rag1 and Rag2 induction following IL-7 withdrawal (Fig. 8c).
0.92 Rag1 and Rag2 expression (Fig. 7a), Id3 ablated detectable Igkappa germline transcription (Fig. 7b).
0.57 Rag1 and Rag2 was not altered in Id3-/- pre-B cells as compared to WT cells (Fig. 7e); furthermore, Ccnd2, Ccnd3 and Ccne expression was comparable between WT and Id3-/- cells (Supplementary Fig. 6).
26477367 0.98 RAG1 protein, which harbors the endolytic activity, functions in conjunction with RAG2, a co-factor that is essential for recombinase activity.
0.97 RAG1 and RAG2 (the protein products of the recombination activating genes 1 and 2).
0.97 RAG1 is bound without RAG2 it binds in an RSS specific manner and is not found at H3K4me3 enriched promoters.
0.96 RAG1 and RAG2 overlaps with that of H3K4me3.
0.90 RAG1-RAG2 heterotetramer is Y-shaped, with a RAG1-RAG2 heterodimer constituting each arm.
0.64 RAG2 protein and the second involves control of Rag1 expression.
22984564 0.98 RAG-1 and RAG-2) encode a V(D)J recombinase responsible for rearrangements of antigen-receptor genes during T and B cell development, and RAG expression is known to correlate strictly with the process of rearrangement.
0.98 RAG-1 and RAG-2 is due to the activity of cis-regulatory elements located in the region 90 kbp upstream of RAG-2 .
0.97 RAG-1) and RAG-2 are closely linked genes encoding two subunits of the lymphocyte-specific RAG recombinase, which is indispensable for the V(D)J recombination responsible for the diversity of immunoglobulins (Igs) and T cell receptors (TCRs).
0.84 RAG-2 expression in the central nervous system was put forth in a study showing expression of RAG-1 transcripts in neurons, but the evidence was not convincing.
0.51 RAG-1, the expression of RAG-2 was not previously detected during any other stage of lymphopoiesis or in any other normal tissue.
24058175 0.98 RAG1, Igkappa germline transcription and RAG1/RAG2 expression are followed by Vkappa assembly and subsequent Igkappa protein expression.
0.97 RAG-1 and RAG-2 genes and Igkappa locus germ line transcription (preludes to Igkappa gene assembly), both being processes mediated by pre-BCR signals, occurred at equivalent levels whether Emu was present or absent on the expressed Igmu allele (Fig. 6).
0.94 RAG2 transcripts (both essential for subsequent Vkappa-Jkappa recombination) were present in comparable levels in the pre-B cells from VHEmua/WTb RAG1-/- and VHDeltaa/WTb RAG1-/- mice.
0.84 RAG1-/- mice were positive for RAG2 transcripts (Fig. 6A, right panel), since these are pro-B cells poised to undergo D-JH and VH-DJH recombination but unable to do so because of the absence of RAG1.
0.81 RAG-1 and RAG-2).
25543141 0.98 RAG-1, in complex with RAG-2(388/405A18), is stimulable by H3K4me3 in a PHD-dependent manner (Fig. S4C).
0.97 RAG-1 and RAG-2, which together cleave DNA at recombination signal sequences (RSSs) that flank the participating gene segments.
0.96 RAG-1 (flR1-MH; Fig. 1D), in complex with RAG-2(388/405A18) or RAG-2(388/405A18, W453A), exhibits increased basal nicking activity relative to a complex with RAG-2(W453A) (Fig. S4C).
0.93 RAG-1 and RAG-2.
0.67 RAG-1 and full-length RAG-2 are largely insoluble.
28867784 0.98 RAG1, RAG2).
0.98 Rag1 and Rag2 expression in a similar fashion in primary mouse pre-B cells and pro-B cells.
0.97 RAG1/2 seem to be coordinately regulated at the transcriptional level, post-transcriptional regulation differs, as, unlike RAG1, RAG2 is subject to cell-cycle-dependent periodic degradation.
0.89 RAG1 and RAG2 Expression and Activity
0.85 RAG1 and RAG2 Expression
31457047 0.98 RAG1 and RAG2, which play an important role in the rearrangement and recombination of immunoglobulin and T-lymphocyte-receptor genes during the VDJ recombination process.
0.97 RAG1 and RAG2 genes play an important role in the rearrangement and recombination of immunoglobulin and T-cell receptor genes during the process of V (D) J recombination.
0.97 RAG1 or RAG2 blocks the initiation of V(D)J recombination in mice.
0.90 RAG-1/RAG-2).
0.72 Rag1-/- and Rag2-/- mice, which are characterized by complete absence of T and B cells.
32060399 0.98 RAG1 and RAG2 peaks) (Fig. 6b), consistent with their mutual enrichment at H3K4me3-positive promoter regions.
0.97 RAG2, which was irrespective of the strong presence of RAG1 or not (Fig. 6a).
0.97 RAG1 or RAG2 peaks, both in wild-type and Atm-/- thymocytes (Fig. 6d).
0.81 RAG1 and RAG2 but also in those containing mostly RAG2 (Fig. 6a, b).
0.72 RAG2 has a wide distribution with a strong presence at active promoters displaying the H3K4me3 histone mark, while the presence of RAG1 is more restricted, only co-localizing with a fraction of RAG2 peaks.
19448632 0.98 Rag1 and Rag2 expression and accumulation of unrepaired RAG-generated Igk coding ends (CEs), which activate ATM-dependent signals.
0.97 RAG1 [http://www.signaling-gateway.org/molecule/query?afcsid=A002009] and RAG2 [http://www.signaling-gateway.org/molecule/query?afcsid=A002010] mediates synapse formation and introduces DNA double-strand breaks (DSBs) between the two participating gene segments and their flanking RSSs.
0.96 RAG1-RAG2 recombinase and was rescued in Rag1-/- developing B cells with a transgene expressing a RAG1 active site mutant that supports DNA binding but not cleavage.
0.92 Rag1 and Rag2 are normal, but both Igh contraction and VH-to-DJH rearrangement of mid and distal VH genes are substantially impaired.
29495457 0.98 Rag2 and Rag1 proteins, which can create DNA double-strand breaks at conserved recombination signal sequences, thus contributing to the development of both B- and T-lymphocytes.
0.95 Rag2 KO and Rag1 KO mice show alteration in behavioral patterns, especially in the stress and fear responses and impairments in social recognition memory, the Rag2 and Rag1 genes play roles mainly by contributing to the learning and memory processes along with the development and functioning of the central nervous system.
0.95 Rag2 KO and Rag1 KO mice might be the result of the deregulation of the miRNA-dependent l-tryptophan metabolism pathways.
0.76 Rag2/Rag1-deficient mice.
15173209 0.98 Rag1, Rag2, and terminal deoxynucleotidyl transferase [TdT]), thereby preventing further rearrangement on the second HC allele.
0.98 Rag2-/- pro-B cells can mediate down-regulation of TdT, Rag1, and probably Rag2, providing a model that could explain how the mechanisms involved in the establishment of allelic exclusion are still functional in the absence of SLC and, therefore, a conventional pre-BCR.
0.97 Rag2-/- pro-B cells induces down-regulation of the following: (a) TdT protein, (b) a transgenic green fluorescent protein reporter reflecting endogenous Rag2 expression, and (c) Rag1 primary transcripts.
21695116 0.98 Rag1 and Rag2 proteins form a complex with DNA to configure a hairpin structure necessary for the endonuclease activity of Artemis.
0.88 Rag1-/-gammac-/- mice as compared to Rag2-/-gammac-/- mice.
0.54 Rag1 or Rag2 mutations as is commonly seen in Prkdc-/- mice.
22224778 0.98 RAG1 and RAG2 proteins, which are expressed primarily in developing lymphocytes.
0.98 RAG1, both RAG1 and RAG2 are required for DNA cleavage.
0.98 RAG1 and RAG2 are expressed primarily in developing lymphocytes.
23965619 0.98 Rag1 and Rag2 expression in the BM and spleen, as well as the gut LP (Supplementary Fig. 15).
0.97 RAG1/RAG2 endonuclease ("RAG") initiates the V(D)J recombination reaction that assembles Ig heavy (IgH) and light (IgL) chain variable region exons from germline gene segments to generate primary antibody repertoires.
0.90 Rag1 and Rag2 expression in wild type small intestinal LP at a level of about 1-10% that of total bone marrow (BM), but little or no Rag1 or Rag2 expression in mLN or IEL cells (Supplementary Fig. 1), confirming the flow cytometry results found with the Rag2-Gfp reporter mice.
26018782 0.98 RAG2 (and potentially RAG1) to bind to transcriptionally active sites outside of antigen receptor loci raises questions about specificity and fidelity of V(D)J recombination.
0.97 RAG2 recruitment mirrors the footprint of the H3K4me3 activation mark, binding to thousands of sites throughout the genome (Figure 1B), whereas RAG1 binding is more directed and occurs predominantly at conserved RSSs.
0.96 RAG1 and RAG2 (collectively known as RAG) function as 'Y-shaped' heterotetramer consisting of two subunits each of RAG1 and RAG2, where the RAG1 subunits contain the endonuclease catalytic center (necessary for cleavage), and is only active in the presence of its binding partner RAG2.
11120771 0.98 recombination activating gene (RAG)1 and RAG2, which together initiate V(D)J recombination by recognizing and cleaving the recombination signal sequences that flank different V, D, and J coding segments (for a review, see reference 1).
0.96 RAG1 and RAG2 are coordinately expressed during B cell development, as sequential IgH D to JH and VH to DJH occurs in B220loCD43+IgM- progenitor B cells, and IgL VL to JL rearrangements take place in B220loCD43loIgM- precursor B cells 2 3 4 5 6.
11560990 0.98 RAG-1 and RAG-2 genes 21.
0.97 RAG-1 or RAG-2 exhibit a developmental block at the DN3 stage due to the inability to rearrange the TCR genes 1.
19395319 0.98 RAG1 and RAG2.
0.92 RAG1 or RAG2.
28352127 0.98 RAG1 and RAG2 are involved in activating the recombination of T-cell receptor molecules and immunoglobulin genes, and a null mutation of either of these genes results in adaptive immunity deficiencies, with an absence of mature B and T lymphocytes.
0.95 RAG1 or RAG2 proteins, Rag1 and Rag2, are susceptible to diet-induced hyperglycaemia.
10859336 0.98 RAG1 and RAG2) encode a lymphocyte-specific enzyme that catalyzes V(D)J recombination 1 2 3.
18768869 0.98 RAG1 and RAG2 genes, which encode the lymphoid-specific components of the V(D)J recombinase responsible for generating T cell receptor (TCR) and immunoglobulin (Ig) diversity in developing T and B lymphocytes.
26843989 0.98 RAG1 is the key endonuclease of V(D)J recombination in immune cells introducing, together with RAG2, DSBs in antigen receptor genes at their RSSs.
30158115 0.98 Rag1 and Rag2 transcription through phosphatidylinositol-3-OH kinase (PI3K) activation, AKT phosphorylation, and Foxo1 inactivation.
30671102 0.98 RAG-2 forms a complex with its partner RAG-1, stabilizing and extending interaction of Rag-1 with the recombination signal sequence which exists adjacent to each V, D, and J segment for correct cleavage of the genes.
24415779 0.97 Rag1 (Rag1C/C) or Rag2 (Rag2C/C) exhibit lymphopenia, reflecting impaired V(D)J recombination and lymphocyte development.
0.97 RAG1/RAG2 endonuclease generates Ag receptor diversity by recombining germline variable (V), diversity (D), and joining (J) gene segments of T cell receptor (TCR) and immunoglobulin (Ig) loci.
0.97 RAG1 and RAG2 proteins are each comprised of core endonuclease domains, defined as the minimal sequences required for DNA cleavage in vitro, and non-core regions that modulate this activity.
0.97 Rag1C/C and Rag2C/C mice each display reduced numbers of mature T and B cells, reflecting impaired lymphocyte development beyond the progenitor stages associated with reduced TCRbeta and IgH recombination).
0.97 Rag1C/C mice display reduced levels of both D-to-J and V-to-DJ recombination of TCRbeta and IgH loci (, Rag2C/C mice show predominantly decreased V-to-DJ rearrangements associated with altered Vbeta/VH usage.
0.97 RAG1/RAG2 proteins in D/J recombination centers capture accessible V RSSs to mediate V-to-(D)J rearrangements.
0.97 RAG1 or RAG2 mutations that diminish RAG endonuclease activity cause inefficient TCR gene assembly, reduced numbers of alphabeta T cells beyond the progenitor stage, restricted TCRbeta and TCRalpha repertoires, and immunodeficiency, revealing that efficient V(D)J recombination is critical for generation of alphabeta TCR diversity.
0.97 RAG1 may have co-evolved with the non-core RAG2 domain and Vbeta RSS sequences to protect host organisms from pathogens by promoting sufficient TCRbeta gene diversity and advantageous representation of individual Vbeta segments in the naive alphabeta TCR repertoire.
0.96 RAG1 or RAG2 mutations that alter or delete non-core RAG1 or RAG2 region amino acids and reduce overall V(D)J recombinase activity cause Omenn Syndrome (OS) or other fatal severe combined immunodeficiencies associated with oligoclonal TCR repertoire and increased T cell mediated autoimmunity.
0.96 Rag2 region, absence of non-core RAG1 regions decreases Vbeta-to-Jbeta recombination and alters the primary Vbeta repertoire generated during Vbeta-to-DJbeta recombination.
0.95 Rag1C/C and Rag2C/C mice compared to WT mice (; Fig. 3 E and F).
0.94 Rag2C/C and Rag1C/C mice.
0.92 Rag1C/C mice, which we have shown exhibit substantial defects in both Dbeta-to-Jbeta and Vbeta-to-DJbeta recombination and altered Vbeta repertoire, Rag2C/C mice have a major impairment in only Vbeta-to-DJbeta recombination that is associated with altered Vbeta usage).
0.85 Rag1C/C mice display reduced D-to-J and V-to-DJ rearrangements of TCRbeta and IgH loci, while Rag2C/C mice show decreased V-to-DJ rearrangements and altered Vbeta/VH repertoire.
30936486 0.97 Rag1 and Rag2 render mice deficient in B and T cells, and mutation of Il2rg is associated with reduced lymphocytes and an absence of NK cells, innate lymphoid cells, and gut-associated lymphoid tissue.
0.95 Rag2-/-Il2rg-/- mice, but not FFT from WT or Rag1-/- mice, indicating that this factor mediated protection even in recipient mice lacking a microbiota (Fig. 2e).
0.91 Rag1-/- mice showed a shift towards Rag2-/-Il2rg-/- mice, treatment with FFT did not alter bacterial communities in Rag1-/- mice, suggesting that MNoVCR6-protection did not depend on alterations to recipient commensal bacteria (Supplementary Fig. 2a,b).
0.90 Rag2-/-Il2rg-/- and controls (Supplementary Fig. 3a), murine astrovirus (muAstV) was identified as the predominant RNA virus only in Rag2-/-Il2rg-/- and Rag1-/- mice (Fig. 3a).
0.85 Rag2-/-Il2rg-/- donors transplanted to Rag1-/-, but not WT, recipients protected them from MNoVCR6 infection (Fig. 2d).
0.76 Rag1-/- mice were cohoused with Rag2-/-Il2rg-/- mice, Rag1-/- mice developed protection against MNoVCR6 (Fig. 2b).
0.75 Rag2-/-Il2rg-/- mice or after FFT in Rag1-/- mice did not induce intestinal inflammation, evidenced by the lack of inflammatory cell infiltration or tissue damage (Fig. 4f).
0.74 Rag1-/- mice were colonized with a viral strain similar to previously described STL1, Rag2-/-Il2rg-/- mice were colonized with two distinct strains, one similar to STL1 and one novel strain, which we designated STL5 (Fig. 3b).
0.61 Rag1-/- and Rag2-/-Il2rg-/- mouse strains with persistent enteric murine norovirus strain MNoVCR6, a model pathogen for human norovirus infection.
31057716 0.97 Rag1 and Rag2 genes are essential for generation of mature B and T lymphocytes.
0.97 Rag1 and Rag2 genes play an important role in the rearrangement and recombination of immunoglobulin and T-cell receptor genes during the process of V(D)J recombination.
0.96 RAG-1 and RAG-2 deficiency, deletion of the Rag-1/Rag-2 genes cause the arrest of rearrangement of B-cell receptors (Immunoglobulin production) and T-cell receptors and lack of the T and B cell differentiation.
0.92 Rag1/Rag2 genes in the NIH/3T3 mouse cell line.
0.87 Rag1/Rag2 genes demonstrate that CRISPR/Cas9 system represents an effective and potential genome editing tool in NIH/3T3 cell line.
0.87 Rag1/Rag2 gene targeting by CRISPR/Cas9 system makes deletions one-step in about 50% of cell lines.
0.85 RAG1/RAG2) immunodeficient mouse models.
0.67 Rag1 and Rag2 genes in NIH/3T3 cell lines.
0.53 RAG-1/RAG-2 deficient mice do not produce mature B and T lymphocytes.
29069605 0.97 RAG1 and RAG2 that bind at well-defined recombination signal sequences (RSSs) flanking each coding V, D, or J gene segment.
0.95 RAG1 protein that specifically recognizes these sequences and catalyzes DNA cleavage at the border of the RSS and the coding gene segment, RAG2 is an equally essential accessory protein.
0.93 RAG2 protein and control of Rag1 expression across the cell cycle contribute; however, these mechanisms do not deal with the issue of how RAG activity is regulated in individual cells.
0.92 RAG1 and RAG2 are dispensable for the joining phase of the V(D)J recombination reaction and thus RAG2-S365 is not involved in repair.
0.89 RAG1 or RAG2 abrogates V(D)J recombination, resulting in severe immunodeficiency.
0.70 RAG2 that might be required for DNA binding by the RAG1/RAG2 complex in in vitro cleavage, nicking, hairpin formation, and pre-cleavage substrate/enzyme stability assays that used a 12-RSS signal substrate.
31380000 0.97 RAG1, RAG2 and IL2RG genes that are involved in immune system functions.
0.96 RAG1, crRNA RAG2-1 and crRNA RAG2-2 are active and crRNA-guided Cas9 specifically cleaves target DNA sequences of RAG1 and RAG2 gene fragments.
0.90 RAG1, RAG2 and IL2RG genes.
0.76 RAG1, RAG2 and IL2RG mouse genes.
0.70 RAG1, RAG2, IL2RG genes in vitro
0.53 RAG1, RAG2 and IL2RG genes.
22374983 0.97 Rag2-/- gammac-/- mice with Rag1-/- bone marrow renders them resistant to challenge with IL15-secreting cancer cells.
0.95 Rag2-/-gammac-/- mice that received Rag1-/- BM.
0.88 Rag1-/- bone marrow can eradicate established M-IL15 tumors in Rag2-/-gammac-/- mice.
0.87 Rag2-/- gammac-/- mice reconstituted with Rag1-/- bone marrow were resistant to outgrowth of M-IL15 cancer cells (Fig. 3A).
0.68 Rag1-/- bone marrow cells causes regression of M-IL15 tumors in Rag2-/- gammac-/- mice
11602643 0.97 RAG-1 and RAG-2 28.
0.97 RAG-1- or RAG-2-deficient mice B and T cell development are blocked at an early progenitor stage 29 30.
0.97 RAG-1 or RAG-2 in B and T cell progenitors in the BM can thus be expected to lead to a block in B and T cell generation.
0.81 RAG-1 and RAG-2 knockout mice (29 30; data not shown).
18375979 0.97 Rag1 and Rag2 proteins initiate V(D)J recombination by introducing site-specific DNA double-strand breaks.
0.97 Rag1 that are specifically required for transesterification and suggest an unexpected role for Rag2 in DNA cleavage and transposition.
0.94 Rag1 mutants, but not Rag2 K38A/R39A, are able to capture target.
0.63 Rag2 K38A/R39A differs from that of the coding flank sensitive Rag1 mutants in two interesting respects.
22770220 0.97 Rag2-/-gammac-/- were significantly lower than in Rag1-/- mice (Figure 3E) and LTi-specific CD30 ligand (Cd30l) mRNA was profoundly reduced (Figure 3F), suggesting an involvement of LTi cells in the generation of Mfge8+ cells.
0.91 Rag1-/-, and microMTD spleens the reduction was less pronounced than in Lta-/-, Ltb-/-, Ltbr-/-, and Rag2-/-gammac-/- mice, suggesting that FDC maturation was arrested at a later stage.
0.81 Rag2-/-gammac-/- had significantly reduced levels of Lta compared to Rag1-/-.
0.80 Rag1-/-,and Rag2-/-gammac-/- spleens (n = (2-3) x 3).Compared to Rag1-/-Cd30l is significantly reduced in Rag2-/-gammac-/- spleens.
25259923 0.97 RAG1 and RAG2 (collectively, RAG) mediate V(D)J gene rearrangement at the antigen receptor loci during lymphocyte development, giving rise to lymphocytes with unique specificity and providing the molecular mechanism behind Burnet's theory of clonal selection.
0.97 RAG1 contains the endonuclease catalytic center, which is active in the presence of its binding partner RAG2.
0.96 RAG1 protein expressed by these bacterial artificial chromosome transgenic mice lacks DNA cleavage activity but interacts with RAG2 and binds DNA normally.
0.96 Rag1-/- and Rag2-/- NK cells, NK cells from Rag1-/- D708A mice exhibited an activated and terminally-differentiated phenotype at steady state and in mixed bone marrow chimeras (Figure 6F and data not shown).
26833222 0.97 RAG1 and RAG2 (forming the RAG endonuclease) introduce double-strand breaks (DSBs) between V, D or J coding gene segments and flanking recombination signal sequences (RSSs).
0.97 RAG1 and RAG2 that are capable of cleavage in vitro but exhibit defects in performing V(D)J recombination of episomal substrates in vivo provided further evidence that the RAG PCC might serve a crucial function in joining coding and signal ends.
0.97 RAG1 and RAG2 proteins might be implicated in the joining step of V(D)J recombination.
0.97 RAG1 and RAG2 proteins is not required for recombination of chromosomally integrated substrates in WT v-abl pro-B cells; but whether such activity could contribute to the impact of ATM/RAG deficiency on V(D)J recombination in the absence of XLF remains to be tested.
29576529 0.97 RAG1 and RAG2 initiate IgH gene assembly by introducing DNA breaks at recombination signal sequences (RSSs) associated with each rearranging gene segment.
0.97 RAG1 only when cells co-express RAG2.
0.92 RAG2-expressing cells we found highest levels of RAG1 at DQ52 and JH gene segments corresponding to the RC on both WT (Figure 5B, green bars) and IGCR1-mutated alleles (Figure 5B, red and blue bars).
0.69 RAG1 did not bind to IgH locus in RAG2-deficient control cells with WT IgH alleles (Figure 5B, yellow bars).
30872621 0.97 RAG1) and 2 (RAG2) initiate the process of V(D)J recombination by introducing site-specific DNA cleavage at the junction between the RSSs and the adjacent coding segment.
0.97 RAG1 or RAG2 displayed a complete block in thymocyte development at the DN3 stage, our data support that the R229 residue of Rag2 affects rearrangement of TCRbeta locus.
0.96 RAG1 or RAG2 mutations are associated with defects in V(D)J recombination activity, causing severe immunodeficiency with a wide spectrum of clinical phenotypes.
0.68 RAG1-RAG2 protein complex, missense mutations leading to SCID or OS can be categorized into four groups: (1) mutations destabilizing the tertiary structure of RAG1-RAG2; (2) mutations affecting polar residues involved in DNA binding; (3) mutations surrounding the active sites; and (4) mutations located at the interface of RAG1 and RAG2.
31350389 0.97 Rag1-H3K36me3 and Rag2-H3K4me3 may play differential roles at different segments during V(D)J recombination at TCRbeta loci.
0.96 Rag1 and Rag2.
0.96 Rag1 or Rag2 expression but rather, at least partially, to decreased occupancy of Rag1 on the TCRbeta or Igh genes and subsequent insufficient cleavage at RSSs mediated by the Rag1/2 complex.
0.84 Rag1 and Rag2 were affected by Setd2 knockout.
10432285 0.97 RAG)-1 and RAG-2 4 7 8 9.
0.88 RAG-1 and RAG-2 is one of the earliest signs of positive selection 4 7 8 9.
0.66 RAG-1 transcript in the thymus of RAG-2-/- OT-1 mice.
22581861 0.97 RAG1 and RAG2) play an essential part in recombination, guiding the process from the cleavage phase through to synapsis and repair.
0.97 Rag1 and Rag2) are closely linked, convergently transcribed and share multiple regulatory elements within a 110 kb region, including several lineage specific enhancers.
0.67 Rag1 and Rag2 loci and surrounding genomic region encompassing known regulatory elements Erag and the ASE as well as the newly identified STAT5/H3K27me3 enriched binding site.
24524915 0.97 Rag1-/- mice, the loss of RAG2 in these mice inactivates the variable (diverse) recombination (V[D]J) process of the immunoglobulin and T cell and B cell receptors.
0.95 RAG1, RAG2 has no confirmed expression in the CNS (Supplemental figures 1 and 2) and thus, the impact of its loss should be restricted to peripheral lymphocytes.
0.91 Rag1/Rag2-/- mouse, as well as those examining Rag1-/- mice report deficits in these models when exposed to stressors.
26223192 0.97 Rag1- and Rag2-deficient mice revealed the existence of a minor population of Thy1+ cells in the epidermis that, unlike DETCs, did not express either CD3 or TCRbeta (Fig. 1a).
0.97 Rag1-/- and Rag2-/- mice revealed uniformly high expression of the integrin CD103 (Fig. 1b), a marker normally associated with intraepithelial T cells.
0.58 Rag1 and Rag2 protein from Rosa26Rag1A2 allele as well as express GFP as a reporter of recombination (Fig. S2 and Methods), allowing identification of Rag-expressing cells by flow cytometry (Fig. 5).
21349429 0.97 RAG-1 and RAG-2 initiate rearrangement by cleaving participating gene segments at recombination signal sequences (RSSs).
0.55 RAG-1, wild-type RAG-2 and RAG-2(T490A) supported similar amounts of nicking and transesterification on 12-RSS and 23-RSS substrates; importantly, we observed no difference between wild-type and mutant RAG-2 with respect to off-target nicking or transesterification (Supplemental Fig. S4A).
23900513 0.97 RAG1 and RAG2 (Recombination Activating Genes 1 and 2), which individually harbor many distinct regulatory domains whose functions remain largely enigmatic.
0.92 RAG2 protein and our more recent findings that expression of Rag1 is regulated across cell cycle, there been have no studies that focus specifically on auto-regulation of RAG cleavage activity in individual cells.
25474568 0.97 Rag2/Il2rg mice showed less foot swelling than Rag1-/- mice on day 3 (Fig. 4, Rag2/Il2rg vs Rag1-/-), perhaps suggesting a role for NK cells in promoting edema (a contention proposed previously).
0.93 Rag1-/-, Rag2/Il2rg and NRG).
26887046 0.97 RAG1 and RAG2 proteins form a complex that introduces DNA double strand breaks (DSBs) at the recombination signal sequences (RSSs) that flank the Variable (V), Diversity (D) and Joining (J) gene segments of the immunoglobulin (Ig) and T-cell receptor (TCR) genes, thereby initiating the process of V(D)J recombination that permits expression of Ig and TCR molecules.
0.92 Recombination Activating Gene 1 (RAG1) and RAG2 are critical for T and B cell development.
31134127 0.97 Rag1-/- single gene and Rag2/IL2rg-/- double gene mutated mice.
0.94 Rag1-/- mice, Rag2/IL2rg-/- mice was succumbed to death after C. difficile infection owing to absence of NK cells, Th17, and Th22 cells.
26384565 0.97 Rag1 and Rag2) are crucial in this process through induction of double strand DNA breaks at recombination signal sequences (RSS) flanking each V, D and J gene.
27621418 0.97 RAG1 and RAG2.
29176980 0.96 RAG1 protein is constitutively expressed and functional, while the RAG2 protein, coupled to the estrogen receptor, becomes functionally active upon 4-hydroxytamoxifen (TAM) administration.
0.96 rag1 and rag2-ER transgenes are ubiquitously expressed, that their activity rescues the development of B and T lymphocytes upon TAM-administration, and that this induction is reversible.
0.96 RAG1 and RAG2 overexpression.
0.95 rag1 and rag2-ER are functional transgenes in a non-lymphoid tissue, and that this activity is TAM-inducible.
0.93 rag1and Tg rag2-ER transcripts in Tghi MEF.
29430738 0.95 RAG1 gene is constitutively expressed in the hippocampus, while RAG2 gene expression has not been found in the CNS and is restricted to immature, developing lymphocytes.
0.94 Rag1-/-, Rag2-/- and CD4+ T cell deficient mice on different genetic backgrounds, including C57BL/6 and BALB/c.
0.83 Rag1-/- vs Rag2-/- deficient mice revealed impairments in Rag1-/-, but not Rag2-/- mice, on social recognition memory.
20442785 0.95 RAG-2-/- (Figures 4B-D) and C57BL/6 RAG-1-/- (Figures 4E and 4F) mice with LPS led to significant increases in both parasite length (Figures 4B, 4C and 4E) and egg production (Figure 4D and 4F).
24792912 0.95 Rag1-/-Il10rb-/- mice led to severe colitis, and, similar to Rag2-/-Il10rb-/- recipient mice on the 129SvEv background, was accompanied by a marked reduction in the generation of inducible FOXP3+ Treg cells in the LP (Figure S4C-E).
26926994 0.94 Rag1-/- mice transferred with Rag2+/+ cells (Fig. 2 F).
0.91 Rag1-/- mice showed significantly greater weight loss, colon shortening, and inflammatory scores than Rag1-/- mice receiving Rag2+/+ CD4+ T cells (Fig. 2, B and C).
29875400 0.94 Rag1-/- mice associated with Rag or DKO microbiomes showed that DKO microbiome remained in a stable dysbiotic state, whereas the recipients of "healthy" microbiomes of NHE3-competent donors converged over time to resemble aspects of the NHE3-/--like "inflammatory" dysbiosis.
0.88 Rag and DKO microbiomes in germ-free wild-type mice, we aimed to determine whether we could reproduce the susceptibility to T-cell mediated colitis we recently reported in adoptively-transferred DKO mice using microbiome transplant alone, using germ-free (GF) Rag1-/- mice colonized with the dysbiotic microbiota from DKO mice (Fig. S1C).
27295202 0.94 RAG1, RAG2 function is required during the same T cell receptor rearrangement process initiated by RAG1, thus, Rag2-/- mice also fail to produce mature T cells and B cells.
30228258 0.92 Rag2-/- mice, treatment with an IL-12p40 neutralising antibody, which targets both IL-12 and IL-23, strongly suppressed colonic inflammation in Alpk1-/-Rag1-/- mice, while blocking the IL-23 receptor (IL-23R) only partially reduced pathology (Fig. 2h).
18056287 0.89 RAG1, RAG2:GFP, Tdt, and Igh rearrangements, contain VH cRS SEs.



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