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

Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11577-82. doi: 10.1073/pnas.1932643100. Epub 2003 Sep 19.

Abstract

In the earliest stages of antigen receptor assembly, D and J segments of the Ig heavy chain and T cell receptor beta 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 beta 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • DNA Helicases
  • Histones / chemistry
  • Histones / metabolism*
  • Lysine / metabolism*
  • Methylation
  • Mice
  • Nuclear Proteins / immunology*
  • Nuclear Proteins / metabolism
  • Phosphorylation
  • Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell / immunology*
  • Receptors, Antigen, T-Cell / metabolism
  • Transcription Factors / immunology*
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured
  • VDJ Recombinases / genetics*

Substances

  • Histones
  • Nuclear Proteins
  • Receptors, Antigen, T-Cell
  • Transcription Factors
  • VDJ Recombinases
  • Smarca4 protein, mouse
  • DNA Helicases
  • Lysine