2002
DOI: 10.4049/jimmunol.168.5.2316
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A Change in the Structure of Vβ Chromatin Associated with TCR β Allelic Exclusion

Abstract: To investigate chromatin control of TCR β rearrangement and allelic exclusion, we analyzed TCR β chromatin structure in double negative (DN) thymocytes, which are permissive for TCR β recombination, and in double positive (DP) thymocytes, which are postallelic exclusion and nonpermissive for Vβ to DβJβ recombination. Histone acetylation mapping and DNase I sensitivity studies indicate Vβ and DβJβ segments to be hyperacetylated and accessible in DN thymocytes. However, they are separated from each other by hypo… Show more

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Cited by 73 publications
(66 citation statements)
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“…(V␤14 is marked by similar chromatin modifications, but this may simply be due to its close proximity to E␤.) We also note that a number of V␤ segments have been found to be acetylated in developing RAG-deficient thymocytes (28). However, the apparent difference in our findings might result from analysis of cells at slightly different developmental stages, differences in the particular V␤ segments analyzed, or differences between primary and immortalized cells.…”
Section: Inverse Correlation Of Acetyl H3 and Di-me H3-k9 At Antigen contrasting
confidence: 47%
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“…(V␤14 is marked by similar chromatin modifications, but this may simply be due to its close proximity to E␤.) We also note that a number of V␤ segments have been found to be acetylated in developing RAG-deficient thymocytes (28). However, the apparent difference in our findings might result from analysis of cells at slightly different developmental stages, differences in the particular V␤ segments analyzed, or differences between primary and immortalized cells.…”
Section: Inverse Correlation Of Acetyl H3 and Di-me H3-k9 At Antigen contrasting
confidence: 47%
“…However, recent work suggests that the localized changes in chromatin structure induced by cis-acting regulatory elements, rather than transcription itself, are critical for establishing a recombination-accessible chromatin state (17). In addition, the transcription factors E2A and EBF, in conjunction with the recombinase, are sufficient to permit endogenous gene rearrangements in a nonlymphoid cell line, an effect likely due to changes in chromatin structure (18,19).A strong correlation between histone acetylation (or factors that increase acetylation) and a recombinationally accessible chromatin state has been shown in vivo (12,(20)(21)(22)(23)(24)(25)(26)(27)(28), including the mapping of acetylated histone H3 and H4 to recombinationally accessible gene segments at a series of loci. In vitro, RAG proteins cannot cleave unmodified nucleosomal DNA (22,29,30), but acetylation and hSWI͞SNF remodeling render nucleosomal DNA accessible for cleavage (31).…”
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confidence: 99%
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“…1). The analogous V-D region in the Tcr␤ locus contains a trypsinogen gene, which is expressed in pancreas but not in T cells (46). These findings eliminate the possibility that ADAM6 plays a role in stromal cell-pro-B cell adhesion.…”
Section: Discussionmentioning
confidence: 51%
“…This loss in V␤ segment activation is measured by decreased germline transcription, decreased histone H3 and H4 acetylation, decreased histone H3 lysine 4 (K4) methylation, and decreased sensitivity to nuclease digestion (7)(8)(9). This loss in V␤ accessibility no doubt contributes to feedback inhibition and allelic exclusion.…”
mentioning
confidence: 99%