1. Structural insights into the cooperative nucleosome recognition and chromatin opening by FOXA1 and GATA4.
- Author
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Zhou, Bing-Rui, Feng, Hanqiao, Huang, Furong, Zhu, Iris, Portillo-Ledesma, Stephanie, Shi, Dan, Zaret, Kenneth S., Schlick, Tamar, Landsman, David, Wang, Qianben, and Bai, Yawen
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TRANSCRIPTION factors , *CELL determination , *LIVER cells , *CELL physiology , *CHROMATIN - 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. [Display omitted] • FOXA1 binds linker DNA, whereas GATA4 targets an internal site within the nucleosome • The IDRs of FOXA1 and GATA4 interact with the acidic patch in H2A/H2B • FOXA1 enhances GATA4 binding by nucleosome repositioning-mediated cooperativity • FOXA1 and GATA4 open chromatin by disrupting H1 binding and nucleosome packing FOXA1 and GATA4 are prototype pioneer factors. Zhou et al. determined the cryo-EM structures of the native N1 nucleosome bound to FOXA1 or GATA4 or both. The authors provide insights into the binding modes, illustrating that the two pioneer factors work cooperatively to open chromatin by disrupting nucleosome packing. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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