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A shared Runx1-bound Zbtb16 enhancer directs innate and innate-like lymphoid lineage development

Author

Listed:
  • Ai-Ping Mao

    (University of Chicago
    University of Chicago)

  • Isabel E. Ishizuka

    (University of Chicago
    University of Chicago)

  • Darshan N. Kasal

    (University of Chicago
    University of Chicago)

  • Malay Mandal

    (University of Chicago
    University of Chicago)

  • Albert Bendelac

    (University of Chicago
    University of Chicago)

Abstract

Zbtb16-encoded PLZF is a signature transcription factor (TF) that directs the acquisition of T-helper effector programs during the development of multiple innate lymphocyte lineages, including natural killer T cell, innate lymphoid cell, mucosal-associated invariant T cell and γδ lineages. PLZF is also essential in osteoblast and spermatogonial development. How Zbtb16 itself is regulated in different lineages is incompletely understood. Here, by systematic CRISPR/Cas9-assisted deletions of chromatin accessible regions within the Zbtb16 locus in mouse, we identify a critical enhancer controlling PLZF expression exclusively in innate lymphoid lineages. Multiple sites within this enhancer express canonical motifs for the TF Runx1, which is essential for the development of these lineages. Notably, some regulatory sites control the kinetic rather than the overall level of PLZF expression. Thus, our comprehensive, unbiased analysis of regulatory elements in vivo reveals critical mechanisms of Zbtb16 regulation shared between innate and innate-like lymphoid lineages.

Suggested Citation

  • Ai-Ping Mao & Isabel E. Ishizuka & Darshan N. Kasal & Malay Mandal & Albert Bendelac, 2017. "A shared Runx1-bound Zbtb16 enhancer directs innate and innate-like lymphoid lineage development," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00882-0
    DOI: 10.1038/s41467-017-00882-0
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    Cited by:

    1. Guillem Sanchez Sanchez & Maria Papadopoulou & Abdulkader Azouz & Yohannes Tafesse & Archita Mishra & Jerry K. Y. Chan & Yiping Fan & Isoline Verdebout & Silvana Porco & Frédérick Libert & Florent Gin, 2022. "Identification of distinct functional thymic programming of fetal and pediatric human γδ thymocytes via single-cell analysis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

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