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Structural insights into the cooperative nucleosome recognition and chromatin opening by FOXA1 and GATA4

  1. Author:
    Zhou, Bing-Rui
    Feng, Hanqiao
    Huang, Furong
    Zhu, Iris
    Portillo-Ledesma, Stephanie
    Shi,Dan
    Zaret, Kenneth S
    Schlick, Tamar
    Landsman, David
    Wang, Qianben
    Bai, Yawen

  2. Author Address

    Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: bing-rui.zhou@nih.gov., Department of Pathology and Duke Cancer Institute, Duke University School of Medicine, Durham, NC 27710, USA., National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20892, USA., Department of Chemistry, New York University, 100 Washington Square East, Silver Building, New York, NY 10003, USA; Simons Center for Computational Physical Chemistry, New York University, 24 Waverly Place, Silver Building, New York, NY 10003, USA., Center for Structural Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA., Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Penn Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Cell and Development Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Department of Chemistry, New York University, 100 Washington Square East, Silver Building, New York, NY 10003, USA; Simons Center for Computational Physical Chemistry, New York University, 24 Waverly Place, Silver Building, New York, NY 10003, USA; Courant Institute of Mathematical Sciences, New York University, 251 Mercer St., New York, NY 10012, USA; New York University-East China Normal University Center for Computational Chemistry, New York University Shanghai, Shanghai 200122, China., Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: baiyaw@mail.nih.gov.,
    1. Year: 2024
    2. Date: Jul 31
    3. Epub Date: 2024 07 31
  2. Journal: Molecular Cell
  4. Type of Article: Article
  1. Abstract:

    Mouse FOXA1 and GATA4 are prototypes of pioneer factors, initiating liver cell development by binding to the N1 nucleosome in the enhancer of the ALB1 gene. Using cryoelectron microscopy (cryo-EM), we determined the structures of the free N1 nucleosome and its complexes with FOXA1 and GATA4, both individually and in combination. We found that the DNA-binding domains of FOXA1 and GATA4 mainly recognize the linker DNA and an internal site in the nucleosome, respectively, whereas their intrinsically disordered regions interact with the acidic patch on histone H2A-H2B. FOXA1 efficiently enhances GATA4 binding by repositioning the N1 nucleosome. In vivo DNA editing and bioinformatics analyses suggest that the co-binding mode of FOXA1 and GATA4 plays important roles in regulating genes involved in liver cell functions. Our results reveal the mechanism whereby FOXA1 and GATA4 cooperatively bind to the nucleosome through nucleosome repositioning, opening chromatin by bending linker DNA and obstructing nucleosome packing. Published by Elsevier Inc.

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  2. DOI: 10.1016/j.molcel.2024.07.016
  3. PMID: 39121853
  4. PII : S1097-2765(24)00592-6

Library Notes

  1. Fiscal Year: FY2023-2024
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