Sequential Enhancer Sequestration Dysregulates Recombination Center Formation at the IgH Locus.

ABSTRACT: Immunoglobulin heavy-chain (IgH) genes are assembled by DNA rearrangements that juxtapose a variable (V_H), a diversity (D_H), and a joining (J_H) gene segment. Here, we report that in the absence of intergenic control region 1 (IGCR1), the intronic enhancer (Eμ) associates with the next available CTCF binding site located close to V_H81X via putative heterotypic interactions involving YY1 and CTCF. The alternate Eμ/V_H81X loop leads to formation of a distorted recombination center and altered D_H rearrangements and disrupts chromosome conformation that favors distal V_H recombination. Cumulatively, these features drive highly skewed, Eμ-dependent recombination of V_H81X. Sequential deletion of CTCF binding reg

SUBMITTER: Qiu X 

PROVIDER: S-EPMC6003238 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature