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

    Research output: Contribution to journalArticle

    60 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 languageEnglish
    Pages (from-to)384-397.e8
    JournalMolecular Cell
    Volume66
    Issue number3
    DOIs
    Publication statusPublished - 2017 May 4

    Fingerprint

    Nucleosomes
    Histones
    Cryoelectron Microscopy
    Molecular Structure
    Hydroxyl Radical
    Chromatin
    Vertebrates
    DNA
    Proteins

    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

    Cite this

    Bednar, J., Garcia-Saez, I., Boopathi, R., Cutter, A. R., Papai, G., Reymer, A., ... 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

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

    In: Molecular Cell, Vol. 66, No. 3, 04.05.2017, p. 384-397.e8.

    Research output: Contribution to journalArticle

    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
    Bednar J, Garcia-Saez I, Boopathi R, Cutter AR, Papai G, Reymer A et al. Structure and Dynamics of a 197 bp Nucleosome in Complex with Linker Histone H1. Molecular Cell. 2017 May 4;66(3):384-397.e8. https://doi.org/10.1016/j.molcel.2017.04.012
    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. / Structure and Dynamics of a 197 bp Nucleosome in Complex with Linker Histone H1. In: Molecular Cell. 2017 ; Vol. 66, No. 3. pp. 384-397.e8.
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