6M4D

Structural mechanism of nucleosome dynamics governed by human histone variants H2A.B and H2A.Z.2.2

6M4D の概要

• エントリーDOI: 10.2210/pdb6m4d/pdb
• EMDBエントリー: 30076
• 分子名称: Histone H3.1, Histone H4, Histone H2A.V, ... (6 entities in total)
• 機能のキーワード: histone; h2a.z; h2a.z.2.2; nucleosome, nuclear protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 196658.64

構造登録者

Zhou, M.,Dai, L.C.,Li, C.M.,Shi, L.X.,Huang, Y.,Guo, Z.Q. (登録日: 2020-03-06, 公開日: 2020-09-23, 最終更新日: 2025-07-02)

主引用文献

Zhou, M.,Dai, L.,Li, C.,Shi, L.,Huang, Y.,Guo, Z.,Wu, F.,Zhu, P.,Zhou, Z.
Structural basis of nucleosome dynamics modulation by histone variants H2A.B and H2A.Z.2.2.
Embo J., 40:e105907-e105907, 2021

PubMed Abstract: Nucleosomes are dynamic entities with wide-ranging compositional variations. Human histone variants H2A.B and H2A.Z.2.2 play critical roles in multiple biological processes by forming unstable nucleosomes and open chromatin structures, but how H2A.B and H2A.Z.2.2 confer these dynamic features to nucleosomes remains unclear. Here, we report cryo-EM structures of nucleosome core particles containing human H2A.B (H2A.B-NCP) at atomic resolution, identifying large-scale structural rearrangements in the histone octamer in H2A.B-NCP. H2A.B-NCP compacts approximately 103 bp of DNA wrapping around the core histones in approximately 1.2 left-handed superhelical turns, in sharp contrast to canonical nucleosome encompassing approximately 1.7 turns of DNA. Micrococcal nuclease digestion assay reveals that nineteen H2A.B-specific residues, including a ROF ("regulating-octamer-folding") sequence of six consecutive residues, are responsible for loosening of H2A.B-NCPs. Unlike H2A.B-NCP, the H2A.Z.2.2-containing nucleosome (Z.2.2-NCP) adopts a less-extended structure and compacts around 125 bp of DNA. Further investigation uncovers a crucial role for the H2A.Z.2.2-specific ROF in both H2A.Z.2.2-NCP opening and SWR1-dependent histone replacement. Taken together, these first high-resolution structure of unstable nucleosomes induced by histone H2A variants elucidate specific functions of H2A.B and H2A.Z.2.2 in enhancing chromatin dynamics.

PubMed: 33073403
DOI: 10.15252/embj.2020105907

実験手法

ELECTRON MICROSCOPY (4.4 Å)