title: 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.
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.
mesh_terms: D000818:Animals; D004265:DNA Helicases; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D009687:Nuclear Proteins / Q000276:immunology* / Q000378:metabolism; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000276:immunology* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D045567:VDJ Recombinases / Q000235:genetics*
chemical_list: D006657:Histones; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D045567:VDJ Recombinases; C513194:Smarca4 protein, mouse; D004265:DNA Helicases; D008239:Lysine