Chromatin architecture, CCCTC-binding factor, and V(D)J recombination: managing long-distance relationships at antigen receptor loci

Abstract

The rearrangement of T and B lymphocyte Ag receptor loci occurs within a highly complex chromosomal environment and is orchestrated through complex mechanisms. During the past decade, a large body of literature has highlighted the significance of chromatin architecture at Ag receptor loci in supporting the genomic assembly process: in preparation for recombination, these loci tend to contract and form multiple loops that shorten the distances between gene segments and facilitate recombination events. CCCTC-binding factor, CTCF, has received much attention in this regard since it has emerged as an important regulator of chromatin organization and transcription. In this review, we summarize recent work outlining conformational dynamics at Ag receptor loci during lymphocyte development and we discuss the role of CTCF in Ag receptor locus conformation and repertoire development.

Figure 1

Long-distance interactions at antigen receptor loci. Long-distance DNA contacts are depicted for the contracted conformation of the Igh locus in pro-B cells (A), the contracted conformation of the Igk locus in pre-B cells (B) and the 3′ contracted but 5′ extended conformation of the Tcra/Tcrd locus in DP thymocytes (C). Interactions known or presumed to be mediated by CTCF or YY1 are indicated. Transcription and recombination phenotypes of various genetic models are summarized (boxes). Igk interactions involving Sis (45) are not depicted.