The fundamental role of chromatin loop extrusion in physiological V(D)J recombination.

ABSTRACT: The RAG endonuclease initiates Igh V(D)J assembly in B cell progenitors by joining D segments to J_H segments, before joining upstream V_H segments to DJ_H intermediates¹. In mouse progenitor B cells, the CTCF-binding element (CBE)-anchored chromatin loop domain² at the 3' end of Igh contains an internal subdomain that spans the 5' CBE anchor (IGCR1)³, the D_H segments, and a RAG-bound recombination centre (RC)⁴. The RC comprises the J_H-proximal D segment (DQ52), four J_H segments, and the intronic enhancer (iEμ)⁵. Robust RAG-mediated cleavage is restricted to paired V(D)J segments flanked by complementary recombination signal sequences (12RSS and 23RSS)⁶. D segmen

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC6867615 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature