Altered 3D chromatin structure permits inversional recombination at the IgH locus

Xiang Qiu, Fei Ma, Mingming Zhao, Yaqiang Cao, Lillian Shipp, Angela Liu, Arun Dutta, Amit Singh, Fatima Zohra Braikia, Supriyo De, William H. Wood, Kevin G. Becker, Weiqiang Zhou, Hongkai Ji, Keji Zhao, Michael L. Atchison, Ranjan Sen

Research output: Contribution to journalArticlepeer-review

Abstract

Immunoglobulin heavy chain (IgH) genes are assembled by two sequential DNA rearrangement events that are initiated by recombination activating gene products (RAG) 1 and 2. Diversity (DH) gene segments rearrange first, followed by variable (VH) gene rearrangements. Here, we provide evidence that each rearrangement step is guided by different rules of engagement between rearranging gene segments. DH gene segments, which recombine by deletion of intervening DNA, must be located within a RAG1/2 scanning domain for efficient recombination. In the absence of intergenic control region 1, a regulatory sequence that delineates the RAG scanning domain on wild-type IgH alleles, VH and DH gene segments can recombine with each other by both deletion and inversion of intervening DNA. We propose that VH gene segments find their targets by distinct mechanisms from those that apply to DH gene segments. These distinctions may underlie differential allelic choice associated with each step of IgH gene assembly.

Original languageEnglish (US)
Article numbereaaz8850
JournalScience Advances
Volume6
Issue number33
DOIs
StatePublished - Aug 2020

ASJC Scopus subject areas

  • General

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