CTCF-binding elements mediate control of V(D)J recombination

摘要: Immunoglobulin heavy chain (IgH) variable region exons are assembled from V(H), D and J(H) gene segments in developing B lymphocytes. Within the 2.7-megabase mouse Igh locus, V(D)J recombination is regulated to ensure specific diverse antibody repertoires. Here we report mice a key regulatory region, termed intergenic control 1 (IGCR1), which lies between V(H) clusters. Functionally, IGCR1 uses CTCF looping/insulator factor-binding elements and, correspondingly, mediates loops containing distant enhancers. promotes normal B-cell development balances repertoires by inhibiting transcription rearrangement of D(H)-proximal promoting distal segments. maintains ordered lineage-specific V(H)(D)J(H) suppressing joining not joined segments, DJ(H) joins thymocytes, respectively. also required for feedback regulation allelic exclusion proximal V(H)-to-DJ(H) recombination. Our studies elucidate long-sought indicate new role generally expressed protein.