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Mol Cell. 2018 Dec 6;72(5):902-915.e7. doi: 10.1016/j.molcel.2018.09.027. Epub 2018 Nov 1.

Structure of an H1-Bound 6-Nucleosome Array Reveals an Untwisted Two-Start Chromatin Fiber Conformation.

Author information

1
Université Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale (IBS), 38000 Grenoble, France.
2
Université Grenoble Alpes, CNRS UMR 5309, INSERM U1209, Institute for Advanced Biosciences (IAB), Site Santé - Allée des Alpes, 38700 La Tronche, France; Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS, Laboratoire de Biologie et de Modélisation de la Cellule LBMC, 46 Allée d'Italie, 69007 Lyon, France.
3
Université Grenoble Alpes, CNRS UMR 5309, INSERM U1209, Institute for Advanced Biosciences (IAB), Site Santé - Allée des Alpes, 38700 La Tronche, France; Laboratory of the Biology and Pathology of the Eye, Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Albertov 4, 128 00 Prague 2, Czech Republic. Electronic address: jan.bednar@univ-grenoble-alpes.fr.
4
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.
5
Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS, Laboratoire de Biologie et de Modélisation de la Cellule LBMC, 46 Allée d'Italie, 69007 Lyon, France. Electronic address: dimitar.anguelov@ens-lyon.fr.
6
Université Grenoble Alpes, CNRS, CEA, Institut de Biologie Structurale (IBS), 38000 Grenoble, France. Electronic address: carlo.petosa@ibs.fr.
7
Université Grenoble Alpes, CNRS UMR 5309, INSERM U1209, Institute for Advanced Biosciences (IAB), Site Santé - Allée des Alpes, 38700 La Tronche, France; "Roumen Tsanev" Institute of Molecular Biology, Bulgarian Academy of Sciences, Sofia, Bulgaria. Electronic address: stefan.dimitrov@univ-grenoble-alpes.fr.

Abstract

Chromatin adopts a diversity of regular and irregular fiber structures in vitro and in vivo. However, how an array of nucleosomes folds into and switches between different fiber conformations is poorly understood. We report the 9.7 Å resolution crystal structure of a 6-nucleosome array bound to linker histone H1 determined under ionic conditions that favor incomplete chromatin condensation. The structure reveals a flat two-start helix with uniform nucleosomal stacking interfaces and a nucleosome packing density that is only half that of a twisted 30-nm fiber. Hydroxyl radical footprinting indicates that H1 binds the array in an on-dyad configuration resembling that observed for mononucleosomes. Biophysical, cryo-EM, and crosslinking data validate the crystal structure and reveal that a minor change in ionic environment shifts the conformational landscape to a more compact, twisted form. These findings provide insights into the structural plasticity of chromatin and suggest a possible assembly pathway for a 30-nm fiber.

KEYWORDS:

30-nm fiber; chromatin; cryo-EM; crystallography; histone H1; linker histone; nucleosome array

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