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

Author

Listed:
  • Khalid H. Bhat

    (University of Illinois College of Medicine
    Faculty of Agriculture)

  • Saurabh Priyadarshi

    (University of Illinois College of Medicine)

  • Sarah Naiyer

    (University of Illinois College of Medicine)

  • Xinyan Qu

    (University of Illinois College of Medicine
    Medpace)

  • Hammad Farooq

    (University of Illinois Colleges of Engineering and Medicine)

  • Eden Kleiman

    (Scripps Research
    Crown Bioscience)

  • Jeffery Xu

    (Scripps Research
    Brookwood Baptist Health General Surgery Residency)

  • Xue Lei

    (University of Illinois Colleges of Engineering and Medicine
    Sanford Burnham Prebys Medical Discovery Institute)

  • Jose F. Cantillo

    (University of Illinois College of Medicine
    Immunotek)

  • Robert Wuerffel

    (University of Illinois College of Medicine
    10441 Circle Dr. Apt 47C)

  • Nicole Baumgarth

    (Johns Hopkins University)

  • Jie Liang

    (University of Illinois Colleges of Engineering and Medicine)

  • Ann J. Feeney

    (Scripps Research)

  • Amy L. Kenter

    (University of Illinois College of Medicine)

Abstract

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 VH enhancers (EVHs) that collaborate to configure the locus. EVHs engage in a network of long-range interactions that interconnect the subTADs and the recombination center at the DHJH gene cluster. Deletion of EVH1 reduces V gene rearrangement in its vicinity and alters discrete chromatin loops and higher order locus conformation. Reduction in the rearrangement of the VH11 gene used in anti-PtC responses is a likely cause of the observed reduced splenic B1 B cell compartment. EVH1 appears to block long-range loop extrusion that in turn contributes to locus contraction and determines the proximity of distant VH genes to the recombination center. EVH1 is a critical architectural and regulatory element that coordinates chromatin conformational states that favor V(D)J rearrangement.

Suggested Citation

  • Khalid H. Bhat & Saurabh Priyadarshi & Sarah Naiyer & Xinyan Qu & Hammad Farooq & Eden Kleiman & Jeffery Xu & Xue Lei & Jose F. Cantillo & Robert Wuerffel & Nicole Baumgarth & Jie Liang & Ann J. Feene, 2023. "An Igh distal enhancer modulates antigen receptor diversity by determining locus conformation," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36414-2
    DOI: 10.1038/s41467-023-36414-2
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