Loop extrusion mediates physiological Igh locus contraction for RAG scanning.

ABSTRACT: RAG endonuclease initiates Igh V(D)J recombination in progenitor B cells by binding a J_H-recombination signal sequence (RSS) within a recombination centre (RC) and then linearly scanning upstream chromatin, presented by loop extrusion mediated by cohesin, for convergent D-RSSs^1,2. The utilization of convergently oriented RSSs and cryptic RSSs is intrinsic to long-range RAG scanning³. Scanning of RAG from the DJ_H-RC-RSS to upstream convergent V_H-RSSs is impeded by D-proximal CTCF-binding elements (CBEs)^2-5. Primary progenitor B cells undergo a mechanistically undefined contraction of the V_H locus that is proposed to provide distal V_Hs access to the DJ_H-RC^6-9. Here we report that an

SUBMITTER: Dai HQ 

PROVIDER: S-EPMC9037962 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature