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Mol Cell. 2017 May 4;66(3):384-397.e8. doi: 10.1016/j.molcel.2017.04.012.

Structure and Dynamics of a 197 bp Nucleosome in Complex with Linker Histone H1.

Author information

1
Institut for Advanced Biosciences, Inserm U 1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France.
2
Institut de Biologie Structurale (IBS), Université Grenoble Alpes, CEA, CNRS, 38044 Grenoble, France.
3
Institut for Advanced Biosciences, Inserm U 1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France; Université de Lyon, Institut NeuroMyoGène (INMG) CNRS/UCBL UMR5310 & Laboratoire de Biologie et de Modélisation de la Cellule (LBMC) CNRS/ENSL/UCBL, Ecole Normale Supérieure de Lyon, 69007 Lyon, France.
4
Department of Biochemistry and Biophysics, University of Rochester, Rochester, New York 14642, USA.
5
Department of Integrated Structural Biology, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC)/Université de Strasbourg/CNRS/INSERM, 67404 Illkirch Cedex, France.
6
MMSB, University of Lyon I/CNRS UMR 5086, Institut de Biologie et Chimie des Protéines, 69367 Lyon, France.
7
Département de Génomique Fonctionnelle et Cancer, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC)/Université de Strasbourg/CNRS/INSERM, 67404 Illkirch Cedex, France.
8
Laboratory of Structural Biology, Graduate School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
9
Département de Génomique Fonctionnelle et Cancer, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC)/Université de Strasbourg/CNRS/INSERM, 67404 Illkirch Cedex, France. Electronic address: hamiche@igbmc.fr.
10
Department of Biochemistry and Biophysics, University of Rochester, Rochester, New York 14642, USA. Electronic address: jeffrey_hayes@URMC.rochester.edu.
11
Department of Integrated Structural Biology, Institut de Génétique et Biologie Moléculaire et Cellulaire (IGBMC)/Université de Strasbourg/CNRS/INSERM, 67404 Illkirch Cedex, France. Electronic address: patrick.schultz@igbmc.fr.
12
Université de Lyon, Institut NeuroMyoGène (INMG) CNRS/UCBL UMR5310 & Laboratoire de Biologie et de Modélisation de la Cellule (LBMC) CNRS/ENSL/UCBL, Ecole Normale Supérieure de Lyon, 69007 Lyon, France. Electronic address: dimitar.anguelov@ens-lyon.fr.
13
Institut de Biologie Structurale (IBS), Université Grenoble Alpes, CEA, CNRS, 38044 Grenoble, France. Electronic address: carlo.petosa@ibs.fr.
14
Institut for Advanced Biosciences, Inserm U 1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France. Electronic address: stefan.dimitrov@univ-grenoble-alpes.fr.

Abstract

Linker histones associate with nucleosomes to promote the formation of higher-order chromatin structure, but the underlying molecular details are unclear. We investigated the structure of a 197 bp nucleosome bearing symmetric 25 bp linker DNA arms in complex with vertebrate linker histone H1. We determined electron cryo-microscopy (cryo-EM) and crystal structures of unbound and H1-bound nucleosomes and validated these structures by site-directed protein cross-linking and hydroxyl radical footprinting experiments. Histone H1 shifts the conformational landscape of the nucleosome by drawing the two linkers together and reducing their flexibility. The H1 C-terminal domain (CTD) localizes primarily to a single linker, while the H1 globular domain contacts the nucleosome dyad and both linkers, associating more closely with the CTD-distal linker. These findings reveal that H1 imparts a strong degree of asymmetry to the nucleosome, which is likely to influence the assembly and architecture of higher-order structures.

KEYWORDS:

X-ray crystallography; chromatin; cryo-EM; histone H1; hydroxyl radical footprinting; linker histone; nucleosome; protein-DNA crosslinking

PMID:
28475873
PMCID:
PMC5508712
DOI:
10.1016/j.molcel.2017.04.012
[Indexed for MEDLINE]
Free PMC Article

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