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.
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.
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*
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