CTCF-binding elements 1 and 2 in the Igh intergenic control region cooperatively regulate V(D)J recombination.

Mice and humans generate diverse antibody repertoires through a genomic rearrangement process termed “V(D)J recombination” that assembles genetic regions that encode antigen-binding portions of antibodies by cutting and pasting together different combinations of V, D, and J gene segments. V(D)J recombination is strictly controlled to ensure generating a sufficiently large antibody repertoire to recognize any pathogen encountered and to minimize generation of self-reactive antibodies. Across the large antibody heavy-chain locus, V(D)J recombination regulation depends on a small control region, intergenic control region 1 (IGCR1), containing two CCCTC-binding factor–binding elements (CBEs) that bind a broadly expressed factor implicated in chromosomal looping. The current studies show that these two CBEs function cooperatively to mediate full IGCR1 functions and suggest a working model for how they do so.