Extremely Long-Range Chromatin Loops Link Topological Domains to Facilitate a Diverse Antibody Repertoire

Cell Reports
Lindsey MontefioriAmy L Kenter

Abstract

Early B cell development is characterized by large-scale Igh locus contraction prior to V(D)J recombination to facilitate a highly diverse Ig repertoire. However, an understanding of the molecular architecture that mediates locus contraction remains unclear. We have combined high-resolution chromosome conformation capture (3C) techniques with 3D DNA FISH to identify three conserved topological subdomains. Each of these topological folds encompasses a major VH gene family that become juxtaposed in pro-B cells via megabase-scale chromatin looping. The transcription factor Pax5 organizes the subdomain that spans the VHJ558 gene family. In its absence, the J558 VH genes fail to associate with the proximal VH genes, thereby providing a plausible explanation for reduced VHJ558 gene rearrangements in Pax5-deficient pro-B cells. We propose that Igh locus contraction is the cumulative effect of several independently controlled chromatin subdomains that provide the structural infrastructure to coordinate optimal antigen receptor assembly.

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Citations

Mar 26, 2016·Trends in Genetics : TIG·Michael S Krangel
Jun 7, 2016·Cell Reports·Daniel J BollandAnne E Corcoran
Nov 1, 2017·Proceedings of the National Academy of Sciences of the United States of America·Michele Di PierroJosé N Onuchic
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Dec 11, 2019·Briefings in Functional Genomics·Anne van SchoonhovenRalph Stadhouders
Dec 13, 2019·Transcription·E Mauricio Barajas-Mora, Ann J Feeney
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Nov 30, 2018·Frontiers in Immunology·Gita KumariRanjan Sen
Jan 30, 2021·Nature Communications·Roser Vilarrasa-BlasiJosé Ignacio Martin-Subero
Mar 9, 2021·Frontiers in Immunology·Carolyn H RogersAnne E Corcoran
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Jan 18, 2018·Trends in Genetics : TIG·Sören BollerRudolf Grosschedl

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