Format

Send to

Choose Destination
J Biol Chem. 2014 Aug 8;289(32):21844-55. doi: 10.1074/jbc.M114.558940. Epub 2014 Jun 11.

Insight into the architecture of the NuRD complex: structure of the RbAp48-MTA1 subcomplex.

Author information

1
From the School of Molecular Bioscience, University of Sydney, New South Wales 2006, Australia.
2
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
3
Department of Genetics, University of Cambridge, CB2 3EH, United Kingdom.
4
Department of Molecular Cancer Research, UMC Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands, and.
5
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104.
6
From the School of Molecular Bioscience, University of Sydney, New South Wales 2006, Australia, joel.mackay@sydney.edu.au.
7
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom, e.d.laue@bioc.cam.ac.uk.

Abstract

The nucleosome remodeling and deacetylase (NuRD) complex is a widely conserved transcriptional co-regulator that harbors both nucleosome remodeling and histone deacetylase activities. It plays a critical role in the early stages of ES cell differentiation and the reprogramming of somatic to induced pluripotent stem cells. Abnormalities in several NuRD proteins are associated with cancer and aging. We have investigated the architecture of NuRD by determining the structure of a subcomplex comprising RbAp48 and MTA1. Surprisingly, RbAp48 recognizes MTA1 using the same site that it uses to bind histone H4, showing that assembly into NuRD modulates RbAp46/48 interactions with histones. Taken together with other results, our data show that the MTA proteins act as scaffolds for NuRD complex assembly. We further show that the RbAp48-MTA1 interaction is essential for the in vivo integration of RbAp46/48 into the NuRD complex.

KEYWORDS:

Chromatin; Chromatin Structure; Gene Regulation; MTA1; NuRD Complex; Protein Assembly; Protein Structure; RBBP4; RbAp48

PMID:
24920672
PMCID:
PMC4139204
DOI:
10.1074/jbc.M114.558940
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Secondary source ID, Grant support

Publication types

MeSH terms

Substances

Secondary source ID

Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center