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

Jan Bednar 10, Isabel Garcia-Saez 10, Ramachandran Boopathi 10, Amber R. Cutter 10, Gabor Papai 10, Anna Reymer, Sajad H. Syed 9, Imtiaz Nisar Lone, Ognyan Tonchev, Corinne Crucifix, Hervé Menoni, Christophe Papin, Dimitrios A. Skoufias, Hitoshi Kurumizaka, Richard Lavery, Ali Hamiche, Jeffrey J. Hayes, Patrick Schultz, Dimitar Angelov, Carlo Petosa, Stefan Dimitrov 11

9 Present address: Division of Cancer Pharmacology, Indian Institute of Integrative Medicine (CSIR), Canal Road, Jammu-180001, Jammu and Kashmir, India

10 These authors contributed equally

11 Lead Contact

Article Info

Publication History

Published: May 4, 2017; corrected online: May 27, 2017

Accepted: April 17, 2017

Received in revised form: March 8, 2017 Received: September 19, 2016


• Cryo-EM and crystal structures of the nucleosome bound to histone H1 were determined

• H1 binding induces the nucleosome to adopt a more compact and rigid conformation

• The H1 globular domain interacts with core DNA on the dyad and with both DNA linkers

• The H1 C-terminal domain associates primarily with a single DNA linker


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


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