8EVH

CX3CR1 nucleosome and wild type PU.1 complex

8EVH の概要

• エントリーDOI: 10.2210/pdb8evh/pdb
• EMDBエントリー: 28629
• 分子名称: Histone H3.1, Histone H4, Histone H2A type 2-C, ... (8 entities in total)
• 機能のキーワード: nucleosome, transcription factor, transcription, chromatin binding protein-dna complex, dna binding protein-dna complex, transcription-dna complex, transcription/dna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 13
• 化学式量合計: 300490.37

構造登録者

Lian, T.,Guan, R.,Bai, Y. (登録日: 2022-10-20, 公開日: 2023-11-01, 最終更新日: 2024-10-16)

主引用文献

Lian, T.,Guan, R.,Zhou, B.R.,Bai, Y.
Structural mechanism of synergistic targeting of the CX3CR1 nucleosome by PU.1 and C/EBP alpha.
Nat.Struct.Mol.Biol., 31:633-643, 2024

PubMed Abstract: Pioneer transcription factors are vital for cell fate changes. PU.1 and C/EBPα work together to regulate hematopoietic stem cell differentiation. However, how they recognize in vivo nucleosomal DNA targets remains elusive. Here we report the structures of the nucleosome containing the mouse genomic CX3CR1 enhancer DNA and its complexes with PU.1 alone and with both PU.1 and the C/EBPα DNA binding domain. Our structures reveal that PU.1 binds the DNA motif at the exit linker, shifting 17 bp of DNA into the core region through interactions with H2A, unwrapping ~20 bp of nucleosomal DNA. C/EBPα binding, aided by PU.1's repositioning, unwraps ~25 bp of entry DNA. The PU.1 Q218H mutation, linked to acute myeloid leukemia, disrupts PU.1-H2A interactions. PU.1 and C/EBPα jointly displace linker histone H1 and open the H1-condensed nucleosome array. Our study unveils how two pioneer factors can work cooperatively to open closed chromatin by altering DNA positioning in the nucleosome.

PubMed: 38267599
DOI: 10.1038/s41594-023-01189-z

実験手法

ELECTRON MICROSCOPY (2.85 Å)