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Structural basis of nucleosome dynamics modulation by histone variants H2A.B and H2A.Z.2.2
Author(s) -
Zhou Min,
Dai Linchang,
Li Chengmin,
Shi Liuxin,
Huang Yan,
Guo Zhenqian,
Wu Fei,
Zhu Ping,
Zhou Zheng
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2020105907
Subject(s) - nucleosome , histone octamer , micrococcal nuclease , histone , chromatin , histone h2a , linker dna , histone h1 , histone methylation , chromatosome , histone code , biophysics , dna , chemistry , biology , genetics , dna methylation , gene , gene expression
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‐ NCP s. 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 SWR 1‐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.