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Loop extrusion mediates physiological Igh locus contraction for RAG scanning by Hai-Qiang Dai; Hongli Hu; Jiangman Lou; Adam Yongxin Ye; Zhaoqing Ba; Xuefei Zhang; Yiwen Zhang; Lijuan Zhao; Hye Suk Yoon; Aimee M. Chapdelaine-Williams; Nia Kyritsis; Huan Chen; Kerstin Johnson; Sherry Lin; Andrea Conte; Rafael Casellas; Cheng-Sheng Lee; Frederick W. Alt is a scholarly article available to read on EtoBox.

What is Loop extrusion mediates physiological Igh locus contraction for RAG scanning about?

RAG endonuclease initiates Igh V(D)J recombination in progenitor B cells by binding a J-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. The utilization of convergently oriented RSSs and cryptic RSSs is intrinsic to long-range RAG scanning. Scanning of RAG from the DJ-RC-RSS to upstream convergent V-RSSs is impeded by D-proximal CTCF-binding elements (CBEs). Primary progenitor B cells undergo a mechanistically undefined contraction of the V locus that is proposed to provide distal Vs access to the DJ-RC. Here we report that an inversion of the entire 2.4-Mb V locus in mouse primary progenitor B cells abrogates rearrangement of both V-RSSs and normally convergent cryptic RSSs, even though locus contraction still occurs. In addition, this inversion activated both the utilization of cryptic V-RSSs that are normally in opposite orientation and RAG scanning beyond the V locus through several convergent CBE domains to the telomere. Together, these findings imply that broad deregulation of CBE impediments in primary progenitor B cells promotes RAG sc

Author

Hai-Qiang Dai; Hongli Hu; Jiangman Lou; Adam Yongxin Ye; Zhaoqing Ba; Xuefei Zhang; Yiwen Zhang; Lijuan Zhao; Hye Suk Yoon; Aimee M. Chapdelaine-Williams; Nia Kyritsis; Huan Chen; Kerstin Johnson; Sherry Lin; Andrea Conte; Rafael Casellas; Cheng-Sheng Lee; Frederick W. Alt

Publisher

Springer Science and Business Media LLC

Published

2021

Language

EN