Antigen receptor loci poised for V(D)J rearrangement are broadly associated with BRG1 and flanked by peaks of histone H3 dimethylated at lysine 4

Katrina B. Morshead, David N. Ciccone, Sean D. Taverna, C. David Allis, Marjorie A. Oettinger

Research output: Contribution to journalArticlepeer-review

Abstract

In the earliest stages of antigen receptor assembly, D and J segments of the Ig heavy chain and T cell receptor β loci are recombined in B and T cells, respectively, whereas the V segments are not. Distinct distribution patterns of various histone modifications and the nucleosome-remodeling factor BRG1 are found at "active" (DJ) and "inactive" (V) regions. Striking "hotspots" of histone H3 dimethylated at lysine 4 (di-Me H3-K4) are localized at the ends of the active DJ domains of both the Ig heavy chain and T cell receptor β loci. BRG1 is not localized to specific sequences, as it is with transcriptional initiation, but rather associates with the entire active locus in a pattern that mirrors acetylation of histone H3. Within some inactive loci marked by H3-K9 dimethylation, two distinct levels of methylation are found in a nonrandom gene-segment-specific pattern. We suggest that the hotspots of di-Me H3-K4 are important marks for locus accessibility. The specific patterns of modification imply that the regulation of V(D)J recombination involves recruitment of specific methyltransferases in a localized manner.

Original languageEnglish (US)
Pages (from-to)11577-11582
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number20
DOIs
StatePublished - Sep 30 2003
Externally publishedYes

ASJC Scopus subject areas

  • General

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