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

• Published in: Molecular cell Vol. 66; no. 3; pp. 384 - 397.e8
• Main Authors: Bednar, Jan, Garcia-Saez, Isabel, Boopathi, Ramachandran, Cutter, Amber R., Papai, Gabor, Reymer, Anna, Syed, Sajad H., Lone, Imtiaz Nisar, Tonchev, Ognyan, Crucifix, Corinne, Menoni, Hervé, Papin, Christophe, Skoufias, Dimitrios A., Kurumizaka, Hitoshi, Lavery, Richard, Hamiche, Ali, Hayes, Jeffrey J., Schultz, Patrick, Angelov, Dimitar, Petosa, Carlo, Dimitrov, Stefan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.05.2017; Cell Press
• Subjects: Animals; Annan kemi; Base Pairing; Binding Sites; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; Chemical Sciences; chromatin; Chromatin - chemistry; Chromatin - genetics; Chromatin - metabolism; Chromatin - ultrastructure; Chromatin Assembly and Disassembly; cryo-EM; Cryoelectron Microscopy; DNA - chemistry; DNA - genetics; DNA - metabolism; Fysikalisk kemi; histone H1; Histones - chemistry; Histones - metabolism; Humans; hydroxyl radical footprinting; Life Sciences; linker histone; Models, Molecular; nucleosome; Nucleosomes - chemistry; Nucleosomes - genetics; Nucleosomes - metabolism; Nucleosomes - ultrastructure; Other Chemistry Topics; Physical Chemistry; Protein Binding; Protein Interaction Domains and Motifs; protein-DNA crosslinking; Structure-Activity Relationship; Time Factors; X-ray crystallography; Xenopus laevis - genetics; Xenopus laevis - metabolism; X-ray crystallography; histone H1; nucleosome; linker histone; hydroxyl radical footprinting; chromatin; cryo-EM; protein-DNA crosslinking
• ISSN: 1097-2765; 1097-4164; 1097-4164
• DOI: 10.1016/j.molcel.2017.04.012

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. [Display omitted] •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 Bednar et al. report cryo-EM and crystal structures of a 197 bp nucleosome bound to histone H1, revealing that H1 stabilizes a compact nucleosome conformation. The H1 globular domain binds on the nucleosome dyad, while the C-terminal domain localizes primarily to a single DNA linker, conferring polarity to the nucleosome.