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Sequence logic at enhancers governs a dual mechanism of endodermal organ fate induction by FOXA pioneer factors

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Listed:
  • Ryan J. Geusz

    (University of California, La Jolla
    University of California, La Jolla
    Sanford Consortium for Regenerative Medicine, La Jolla
    University of California San Diego, La Jolla)

  • Allen Wang

    (University of California, La Jolla
    University of California, La Jolla
    Sanford Consortium for Regenerative Medicine, La Jolla)

  • Dieter K. Lam

    (University of California, La Jolla
    University of California, La Jolla
    Sanford Consortium for Regenerative Medicine, La Jolla)

  • Nicholas K. Vinckier

    (University of California, La Jolla
    University of California, La Jolla
    Sanford Consortium for Regenerative Medicine, La Jolla)

  • Konstantinos-Dionysios Alysandratos

    (Center for Regenerative Medicine of Boston University and Boston Medical Center
    Boston University School of Medicine)

  • David A. Roberts

    (Center for Regenerative Medicine of Boston University and Boston Medical Center)

  • Jinzhao Wang

    (University of California, La Jolla
    University of California, La Jolla
    Sanford Consortium for Regenerative Medicine, La Jolla)

  • Samy Kefalopoulou

    (University of California, La Jolla
    University of California, La Jolla
    Sanford Consortium for Regenerative Medicine, La Jolla)

  • Araceli Ramirez

    (University of California, La Jolla
    University of California, La Jolla
    Sanford Consortium for Regenerative Medicine, La Jolla)

  • Yunjiang Qiu

    (University of California, La Jolla)

  • Joshua Chiou

    (University of California, La Jolla
    University of California San Diego, La Jolla)

  • Kyle J. Gaulton

    (University of California, La Jolla)

  • Bing Ren

    (University of California, La Jolla
    Ludwig Institute for Cancer Research, La Jolla)

  • Darrell N. Kotton

    (Center for Regenerative Medicine of Boston University and Boston Medical Center
    Boston University School of Medicine)

  • Maike Sander

    (University of California, La Jolla
    University of California, La Jolla
    Sanford Consortium for Regenerative Medicine, La Jolla)

Abstract

FOXA pioneer transcription factors (TFs) associate with primed enhancers in endodermal organ precursors. Using a human stem cell model of pancreas differentiation, we here discover that only a subset of pancreatic enhancers is FOXA-primed, whereas the majority is unprimed and engages FOXA upon lineage induction. Primed enhancers are enriched for signal-dependent TF motifs and harbor abundant and strong FOXA motifs. Unprimed enhancers harbor fewer, more degenerate FOXA motifs, and FOXA recruitment to unprimed but not primed enhancers requires pancreatic TFs. Strengthening FOXA motifs at an unprimed enhancer near NKX6.1 renders FOXA recruitment pancreatic TF-independent, induces priming, and broadens the NKX6.1 expression domain. We make analogous observations about FOXA binding during hepatic and lung development. Our findings suggest a dual role for FOXA in endodermal organ development: first, FOXA facilitates signal-dependent lineage initiation via enhancer priming, and second, FOXA enforces organ cell type-specific gene expression via indirect recruitment by lineage-specific TFs.

Suggested Citation

  • Ryan J. Geusz & Allen Wang & Dieter K. Lam & Nicholas K. Vinckier & Konstantinos-Dionysios Alysandratos & David A. Roberts & Jinzhao Wang & Samy Kefalopoulou & Araceli Ramirez & Yunjiang Qiu & Joshua , 2021. "Sequence logic at enhancers governs a dual mechanism of endodermal organ fate induction by FOXA pioneer factors," Nature Communications, Nature, vol. 12(1), pages 1-19, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26950-0
    DOI: 10.1038/s41467-021-26950-0
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    1. Laertis Ikonomou & Michael J. Herriges & Sara L. Lewandowski & Robert Marsland & Carlos Villacorta-Martin & Ignacio S. Caballero & David B. Frank & Reeti M. Sanghrajka & Keri Dame & Maciej M. Kańduła , 2020. "The in vivo genetic program of murine primordial lung epithelial progenitors," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    2. Job Dekker & Andrew S. Belmont & Mitchell Guttman & Victor O. Leshyk & John T. Lis & Stavros Lomvardas & Leonid A. Mirny & Clodagh C. O’Shea & Peter J. Park & Bing Ren & Joan C. Ritland Politz & Jay S, 2017. "The 4D nucleome project," Nature, Nature, vol. 549(7671), pages 219-226, September.
    3. Anant Mamidi & Christy Prawiro & Philip A. Seymour & Kristian Honnens Lichtenberg & Abigail Jackson & Palle Serup & Henrik Semb, 2018. "Mechanosignalling via integrins directs fate decisions of pancreatic progenitors," Nature, Nature, vol. 564(7734), pages 114-118, December.
    4. Catherine S. Lee & Joshua R. Friedman & James T. Fulmer & Klaus H. Kaestner, 2005. "The initiation of liver development is dependent on Foxa transcription factors," Nature, Nature, vol. 435(7044), pages 944-947, June.
    5. Danilo Maddalo & Eusebio Manchado & Carla P. Concepcion & Ciro Bonetti & Joana A. Vidigal & Yoon-Chi Han & Paul Ogrodowski & Alessandra Crippa & Natasha Rekhtman & Elisa de Stanchina & Scott W. Lowe &, 2014. "In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system," Nature, Nature, vol. 516(7531), pages 423-427, December.
    6. Yingyao Zhou & Bin Zhou & Lars Pache & Max Chang & Alireza Hadj Khodabakhshi & Olga Tanaseichuk & Christopher Benner & Sumit K. Chanda, 2019. "Metascape provides a biologist-oriented resource for the analysis of systems-level datasets," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    7. Job Dekker & Andrew S. Belmont & Mitchell Guttman & Victor O. Leshyk & John T. Lis & Stavros Lomvardas & Leonid A. Mirny & Clodagh C. O’Shea & Peter J. Park & Bing Ren & Joan C. Ritland Politz & Jay S, 2017. "Correction: Corrigendum: The 4D nucleome project," Nature, Nature, vol. 552(7684), pages 278-278, December.
    8. Adrian Veres & Aubrey L. Faust & Henry L. Bushnell & Elise N. Engquist & Jennifer Hyoje-Ryu Kenty & George Harb & Yeh-Chuin Poh & Elad Sintov & Mads Gürtler & Felicia W. Pagliuca & Quinn P. Peterson &, 2019. "Charting cellular identity during human in vitro β-cell differentiation," Nature, Nature, vol. 569(7756), pages 368-373, May.
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    1. Jianfang Li & Xinwei Wu & Jie Ke & Minjung Lee & Qingping Lan & Jia Li & Jianxiu Yu & Yun Huang & De-Qiang Sun & Ruiyu Xie, 2022. "TET1 dioxygenase is required for FOXA2-associated chromatin remodeling in pancreatic beta-cell differentiation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Yinglei Li & Ran Zheng & Lai Jiang & Chenchao Yan & Ran Liu & Luyi Chen & Wenwen Jin & Yuanyuan Luo & Xiafei Zhang & Jun Tang & Zhe Dai & Wei Jiang, 2024. "A noncoding variant confers pancreatic differentiation defect and contributes to diabetes susceptibility by recruiting RXRA," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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