8VFY

Cryo-EM structure of FoxA1 in complex with ALBN1 nucleosome (class 1)

8VFY の概要

• エントリーDOI: 10.2210/pdb8vfy/pdb
• EMDBエントリー: 43194
• 分子名称: Histone H3.1, Histone H4, Histone H2A type 1-B/E, ... (7 entities in total)
• 機能のキーワード: nucleosome, pioneer transcription factors, dna binding proteins, transcription, chromatin, nuclear protein, nuclear protein-dna complex, nuclear protein/dna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 11
• 化学式量合計: 274714.73

構造登録者

Zhou, B.R.,Bai, Y. (登録日: 2023-12-22, 公開日: 2024-08-07, 最終更新日: 2025-05-21)

主引用文献

Zhou, B.R.,Feng, H.,Huang, F.,Zhu, I.,Portillo-Ledesma, S.,Shi, D.,Zaret, K.S.,Schlick, T.,Landsman, D.,Wang, Q.,Bai, Y.
Structural insights into the cooperative nucleosome recognition and chromatin opening by FOXA1 and GATA4.
Mol.Cell, 84:3061-, 2024

PubMed 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.

PubMed: 39121853
DOI: 10.1016/j.molcel.2024.07.016

実験手法

ELECTRON MICROSCOPY (2.89 Å)