6M4G

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

Summary for 6M4G

• Entry DOI: 10.2210/pdb6m4g/pdb
• EMDB information: 30077
• Descriptor: DNA (93-MER), Histone H3.1, Histone H4, ... (6 entities in total)
• Functional Keywords: histone; variant; h2a.b; nucleosome, nuclear protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 10
• Total formula weight: 197779.26

Authors

Zhou, M.,Dai, L.C.,Li, C.M.,Shi, L.X.,Huang, Y.,Guo, Z.Q. (deposition date: 2020-03-06, release date: 2020-09-23, Last modification date: 2024-03-27)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.8 Å)