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An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation

The mouse Igh locus is organized into a developmentally regulated topologically associated domain (TAD) that is divided into subTADs. Here we identify a series of distal V(H) enhancers (E(VH)s) that collaborate to configure the locus. E(VH)s engage in a network of long-range interactions that interc...

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Autores principales: Bhat, Khalid H., Priyadarshi, Saurabh, Naiyer, Sarah, Qu, Xinyan, Farooq, Hammad, Kleiman, Eden, Xu, Jeffery, Lei, Xue, Cantillo, Jose F., Wuerffel, Robert, Baumgarth, Nicole, Liang, Jie, Feeney, Ann J., Kenter, Amy L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9984487/
https://www.ncbi.nlm.nih.gov/pubmed/36869028
http://dx.doi.org/10.1038/s41467-023-36414-2
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author Bhat, Khalid H.
Priyadarshi, Saurabh
Naiyer, Sarah
Qu, Xinyan
Farooq, Hammad
Kleiman, Eden
Xu, Jeffery
Lei, Xue
Cantillo, Jose F.
Wuerffel, Robert
Baumgarth, Nicole
Liang, Jie
Feeney, Ann J.
Kenter, Amy L.
author_facet Bhat, Khalid H.
Priyadarshi, Saurabh
Naiyer, Sarah
Qu, Xinyan
Farooq, Hammad
Kleiman, Eden
Xu, Jeffery
Lei, Xue
Cantillo, Jose F.
Wuerffel, Robert
Baumgarth, Nicole
Liang, Jie
Feeney, Ann J.
Kenter, Amy L.
author_sort Bhat, Khalid H.
collection PubMed
description The mouse Igh locus is organized into a developmentally regulated topologically associated domain (TAD) that is divided into subTADs. Here we identify a series of distal V(H) enhancers (E(VH)s) that collaborate to configure the locus. E(VH)s engage in a network of long-range interactions that interconnect the subTADs and the recombination center at the D(H)J(H) gene cluster. Deletion of E(VH)1 reduces V gene rearrangement in its vicinity and alters discrete chromatin loops and higher order locus conformation. Reduction in the rearrangement of the V(H)11 gene used in anti-PtC responses is a likely cause of the observed reduced splenic B1 B cell compartment. E(VH)1 appears to block long-range loop extrusion that in turn contributes to locus contraction and determines the proximity of distant V(H) genes to the recombination center. E(VH)1 is a critical architectural and regulatory element that coordinates chromatin conformational states that favor V(D)J rearrangement.
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spelling pubmed-99844872023-03-05 An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation Bhat, Khalid H. Priyadarshi, Saurabh Naiyer, Sarah Qu, Xinyan Farooq, Hammad Kleiman, Eden Xu, Jeffery Lei, Xue Cantillo, Jose F. Wuerffel, Robert Baumgarth, Nicole Liang, Jie Feeney, Ann J. Kenter, Amy L. Nat Commun Article The mouse Igh locus is organized into a developmentally regulated topologically associated domain (TAD) that is divided into subTADs. Here we identify a series of distal V(H) enhancers (E(VH)s) that collaborate to configure the locus. E(VH)s engage in a network of long-range interactions that interconnect the subTADs and the recombination center at the D(H)J(H) gene cluster. Deletion of E(VH)1 reduces V gene rearrangement in its vicinity and alters discrete chromatin loops and higher order locus conformation. Reduction in the rearrangement of the V(H)11 gene used in anti-PtC responses is a likely cause of the observed reduced splenic B1 B cell compartment. E(VH)1 appears to block long-range loop extrusion that in turn contributes to locus contraction and determines the proximity of distant V(H) genes to the recombination center. E(VH)1 is a critical architectural and regulatory element that coordinates chromatin conformational states that favor V(D)J rearrangement. Nature Publishing Group UK 2023-03-03 /pmc/articles/PMC9984487/ /pubmed/36869028 http://dx.doi.org/10.1038/s41467-023-36414-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Bhat, Khalid H.
Priyadarshi, Saurabh
Naiyer, Sarah
Qu, Xinyan
Farooq, Hammad
Kleiman, Eden
Xu, Jeffery
Lei, Xue
Cantillo, Jose F.
Wuerffel, Robert
Baumgarth, Nicole
Liang, Jie
Feeney, Ann J.
Kenter, Amy L.
An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation
title An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation
title_full An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation
title_fullStr An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation
title_full_unstemmed An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation
title_short An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation
title_sort igh distal enhancer modulates antigen receptor diversity by determining locus conformation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9984487/
https://www.ncbi.nlm.nih.gov/pubmed/36869028
http://dx.doi.org/10.1038/s41467-023-36414-2
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