The Nucleosome Remodeling and Deacetylase Complex NuRD Is Built from Preformed Catalytically Active Sub-modules.

Autor: Zhang W; Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom., Aubert A; EMBL Grenoble, 71 avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France., Gomez de Segura JM; EMBL Grenoble, 71 avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France., Karuppasamy M; EMBL Grenoble, 71 avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France., Basu S; Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom., Murthy AS; Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom., Diamante A; Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom., Drury TA; Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom., Balmer J; Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom., Cramard J; Wellcome Trust, Medical Research Council Stem Cell Institute, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge CB2 1QR, United Kingdom., Watson AA; Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom., Lando D; Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom., Lee SF; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom., Palayret M; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom., Kloet SL; Department of Molecular Biology, Radboud Institute of Molecular Life Sciences, M850/3.79 Geert Grooteplein Zuid 30, 6525 GA Nijmegen, the Netherlands., Smits AH; Department of Molecular Biology, Radboud Institute of Molecular Life Sciences, M850/3.79 Geert Grooteplein Zuid 30, 6525 GA Nijmegen, the Netherlands., Deery MJ; Cambridge Centre for Proteomics, Cambridge System Biology Centre, Wellcome Trust Stem Cell building, University of Cambridge, Department of Biochemistry, Tennis Court Road, Cambridge CB2 1QR, United Kingdom., Vermeulen M; Department of Molecular Biology, Radboud Institute of Molecular Life Sciences, M850/3.79 Geert Grooteplein Zuid 30, 6525 GA Nijmegen, the Netherlands., Hendrich B; Wellcome Trust, Medical Research Council Stem Cell Institute, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge CB2 1QR, United Kingdom., Klenerman D; Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom., Schaffitzel C; EMBL Grenoble, 71 avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France; The School of Biochemistry, University of Bristol, University Walk, Clifton BS8 1TD, United Kingdom., Berger I; EMBL Grenoble, 71 avenue des Martyrs, CS 90181, 38042 Grenoble Cedex 9, France; The School of Biochemistry, University of Bristol, University Walk, Clifton BS8 1TD, United Kingdom., Laue ED; Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom.
Jazyk: angličtina
Zdroj: Journal of molecular biology [J Mol Biol] 2016 Jul 17; Vol. 428 (14), pp. 2931-42. Date of Electronic Publication: 2016 Apr 23.
DOI: 10.1016/j.jmb.2016.04.025
Abstrakt: The nucleosome remodeling deacetylase (NuRD) complex is a highly conserved regulator of chromatin structure and transcription. Structural studies have shed light on this and other chromatin modifying machines, but much less is known about how they assemble and whether stable and functional sub-modules exist that retain enzymatic activity. Purification of the endogenous Drosophila NuRD complex shows that it consists of a stable core of subunits, while others, in particular the chromatin remodeler CHD4, associate transiently. To dissect the assembly and activity of NuRD, we systematically produced all possible combinations of different components using the MultiBac system, and determined their activity and biophysical properties. We carried out single-molecule imaging of CHD4 in live mouse embryonic stem cells, in the presence and absence of one of core components (MBD3), to show how the core deacetylase and chromatin-remodeling sub-modules associate in vivo. Our experiments suggest a pathway for the assembly of NuRD via preformed and active sub-modules. These retain enzymatic activity and are present in both the nucleus and the cytosol, an outcome with important implications for understanding NuRD function.
(Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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