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

Jan Bednar; Isabel Garcia-Saez; Ramachandran Boopathi; Amber R. Cutter; Gabor Papai; Anna Reymer; Sajad H. Syed; 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

doi:10.1016/j.molcel.2017.04.012

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

Jan Bednar, Isabel Garcia-Saez, Ramachandran Boopathi, Amber R. Cutter, Gabor Papai, Anna Reymer, Sajad H. Syed, 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 PetosaStefan Dimitrov

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

157 Citations (Scopus)

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.

Original language	English
Pages (from-to)	384-397.e8
Journal	Molecular Cell
Volume	66
Issue number	3
DOIs	https://doi.org/10.1016/j.molcel.2017.04.012
Publication status	Published - 2017 May 4

Keywords

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

ASJC Scopus subject areas

Molecular Biology
Cell Biology

Access to Document

10.1016/j.molcel.2017.04.012

Cite this

Bednar, J., Garcia-Saez, I., Boopathi, R., Cutter, A. R., Papai, G., Reymer, A., Syed, S. H., Lone, I. N., Tonchev, O., Crucifix, C., Menoni, H., Papin, C., Skoufias, D. A., Kurumizaka, H., Lavery, R., Hamiche, A., Hayes, J. J., Schultz, P., Angelov, D., ... Dimitrov, S. (2017). Structure and Dynamics of a 197 bp Nucleosome in Complex with Linker Histone H1. Molecular Cell, 66(3), 384-397.e8. https://doi.org/10.1016/j.molcel.2017.04.012

Bednar, J, Garcia-Saez, I, Boopathi, R, Cutter, AR, Papai, G, Reymer, A, Syed, SH, Lone, IN, Tonchev, O, Crucifix, C, Menoni, H, Papin, C, Skoufias, DA, Kurumizaka, H, Lavery, R, Hamiche, A, Hayes, JJ, Schultz, P, Angelov, D, Petosa, C & Dimitrov, S 2017, 'Structure and Dynamics of a 197 bp Nucleosome in Complex with Linker Histone H1', Molecular Cell, vol. 66, no. 3, pp. 384-397.e8. https://doi.org/10.1016/j.molcel.2017.04.012

@article{85cade0070ae41529b429cf38e4c9738,

title = "Structure and Dynamics of a 197 bp Nucleosome in Complex with Linker Histone H1",

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

author = "Jan Bednar and Isabel Garcia-Saez and Ramachandran Boopathi and Cutter, {Amber R.} and Gabor Papai and Anna Reymer and Syed, {Sajad H.} and Lone, {Imtiaz Nisar} and Ognyan Tonchev and Corinne Crucifix and Herv{\'e} Menoni and Christophe Papin and Skoufias, {Dimitrios A.} and Hitoshi Kurumizaka and Richard Lavery and Ali Hamiche and Hayes, {Jeffrey J.} and Patrick Schultz and Dimitar Angelov and Carlo Petosa and Stefan Dimitrov",

year = "2017",

month = may,

day = "4",

doi = "10.1016/j.molcel.2017.04.012",

language = "English",

volume = "66",

pages = "384--397.e8",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "3",

}

TY - JOUR

T1 - Structure and Dynamics of a 197 bp Nucleosome in Complex with Linker Histone H1

AU - Bednar, Jan

AU - Garcia-Saez, Isabel

AU - Boopathi, Ramachandran

AU - Cutter, Amber R.

AU - Papai, Gabor

AU - Reymer, Anna

AU - Syed, Sajad H.

AU - Lone, Imtiaz Nisar

AU - Tonchev, Ognyan

AU - Crucifix, Corinne

AU - Menoni, Hervé

AU - Papin, Christophe

AU - Skoufias, Dimitrios A.

AU - Kurumizaka, Hitoshi

AU - Lavery, Richard

AU - Hamiche, Ali

AU - Hayes, Jeffrey J.

AU - Schultz, Patrick

AU - Angelov, Dimitar

AU - Petosa, Carlo

AU - Dimitrov, Stefan

PY - 2017/5/4

Y1 - 2017/5/4

N2 - 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.

AB - 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.

KW - chromatin

KW - cryo-EM

KW - histone H1

KW - hydroxyl radical footprinting

KW - linker histone

KW - nucleosome

KW - protein-DNA crosslinking

KW - X-ray crystallography

UR - http://www.scopus.com/inward/record.url?scp=85018756382&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018756382&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2017.04.012

DO - 10.1016/j.molcel.2017.04.012

M3 - Article

C2 - 28475873

AN - SCOPUS:85018756382

SN - 1097-2765

VL - 66

SP - 384-397.e8

JO - Molecular Cell

JF - Molecular Cell

IS - 3

ER -