4.8 Article

Distinct Structures and Dynamics of Chromatosomes with Different Human Linker Histone Isoforms

期刊

MOLECULAR CELL
卷 81, 期 1, 页码 166-+

出版社

CELL PRESS
DOI: 10.1016/j.molcel.2020.10.038

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  1. National Cancer Institute, National Institutes of Health
  2. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health
  3. National Library of Medicine at the US National Institutes of Health
  4. Department of Pathology and Molecular Medicine, Queen's University, Canada
  5. Senior Canada Research Chair in Computational Biology and Biophysics
  6. Ontario Institute of Cancer Research, Canada

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This study used cryo-EM to analyze the structures of chromatosomes containing different H1 isoforms, revealing that the C-terminal tails of the H1 isoforms mainly control the orientations of flanking DNA. The results provide insights into the structures and dynamics of chromatosomes, with implications for the structure and function of chromatin.
The repeating structural unit of metazoan chromatin is the chromatosome, a nucleosome bound to a linker histone, H1 There are 11 human H1 isoforms with diverse cellular functions, but how they interact with the nucleosome remains elusive, Here, we determined the cryoelectron microscopy (cryo-EM) structures of chromatosomes containing 197 bp DNA and three different human H1 isoforms, respectively. The globular domains of all three H1 isoforms bound to the nucleosome dyad. However, the flanking/linker DNAs displayed substantial distinct dynamic conformations. Nuclear magnetic resonance (NMR) and H1 tail-swapping cryo-EM experiments revealed that the C-terminal tails of the H1 isoforms mainly controlled the flanking DNA orientations. We also observed partial ordering of the core histone H2A C-terminal and H3 N-terminal tails in the chromatosomes. Our results provide insights into the structures and dynamics of the chromatosomes and have implications for the structure and function of chromatin.

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