The docking domain of histone H2A is required for H1 binding and RSC-mediated nucleosome remodeling
Manu Shubhdarshan Shukla1,2,a, Sajad Hussain Syed1,2,a, Damien Goutte-Gattat1, John Lalith Charles Richard1,2, Fabien Montel3, Ali Hamiche4, Andrew Travers5,6 Cendrine Faivre-Moskalenko3, Jan Bednar7,8,9, Jeffrey J. Hayes10, Dimitar Angelov2,b and Stefan Dimitrov1,c
1Université Joseph Fourier – Grenoble 1; INSERM Institut Albert Bonniot, U823, Site Santé-BP 170, 38042 Grenoble cedex 9
2Université de Lyon, Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR 5239/INRA 1237/IFR128 Biosciences, École Normale Supérieure de Lyon
3Université de Lyon, Laboratoire de Physique (CNRS UMR 5672), École Normale Supérieure de Lyon, 46 allée d’Italie, 69007 Lyon
4Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Parc d’innovation, 1 rue Laurent Fries, 67404 Illkirch cedec, France
5MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
6Fondation Pierre-Gilles de Gennes pour la Recherche, c/o LBPA, École Normale Supérieure de Cachan, 61 avenue du Président Wilson, 94235 Cachan cedex, France
7Institute of Cellular Biology and Pathology, First Faculty of Medicine, Charles University in Prague
8Department of Cell Biology, Institute of Physiology, Academy of Sciences of the Czech Republic, Albertov 4, 128 01 Prague 2, Czech Republic
9CNRS, Laboratoire de Spectrométrie Physique, UMR 5588, BP87, 140 avenue de la physique, 38402 St. Martin d’Hères cedex, France
10Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester NY 14642, USA
aThe authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.
bCorresponding author: dimitar.anguelov@ens-lyon.fr.
cCorresponding author: stefan.dimitrov@ujf-grenoble.fr.
This article was published in Nucleic Acids Research (NAR) under a Creative Commons Attribution Non-Commercial License.
Nucl. Acids Res., 39(7):2559–2570. [full text]
Abstract
Histone variants within the H2A show high divergences in their C-terminal regions. In this work, we have studied how these divergences and in particular, how a part of the H2A COOH-terminus, the docking domain, is implicated in both structural and functional properties of the nucleosome. Using biochemical methods in combination with Atomic Force Microscopy and Electron Cryo-Microscopy, we show that the H2A-docking domain is a key structural feature within the nucleosome. Deletion of this domain or replacement with the incomplete docking domain from the variant H2A.Bbd results in significant structural alterations in the nucleosome, including an increase in overall accessibility to nucleases, un-wrapping of ~10 bp of DNA from each end of the nucleosome and associated changes in the entry/exit angle of DNA ends. These structural alterations are associated with a reduced ability of the chromatin remodeler RSC to both remodel and mobilize the nucleosomes. Linker histone H1 binding is also abrogated in nucleosomes containing the incomplete docking domain of H2A.Bbd. Our data illustrate the unique role of the H2A-docking domain in coordinating the structural-functional aspects of the nucleosome properties. Moreover, our data suggest that incorporation of a ‘defective’ docking domain may be a primary structural role of H2A.Bbd in chromatin.
Full text
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