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

Insight into the architecture of the NuRD complex: structure of the RbAp48-MTA1 subcomplex
Insight into the architecture of the NuRD complex: structure of the RbAp48-MTA1 subcomplex
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.
0021-9258
21844-21855
Alqarni, Saad S.M.
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Murthy, Andal
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Zhang, Wei
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Przewloka, Marcin
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Silva, Ana P.G.
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Watson, Aleksandra A.
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Lejon, Sara
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Pei, Xue Y.
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Smits, Arne H.
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Kloet, Susan L.
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Wang, Hongxin
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Shepherd, Nicholas E.
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Stokes, Philippa H.
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Blobel, Gerd A.
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Vermeulen, Michiel
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Glover, David M.
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Mackay, Joel P.
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Laue, Ernest D.
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Alqarni, Saad S.M.
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Murthy, Andal
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Zhang, Wei
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Przewloka, Marcin
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Silva, Ana P.G.
abd188a4-945a-42f0-b30f-cbccb2991ae1
Watson, Aleksandra A.
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Lejon, Sara
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Pei, Xue Y.
90e12d57-0a04-450c-8ae9-b0dd058db039
Smits, Arne H.
b664a250-9926-452f-9c32-cfeef899e921
Kloet, Susan L.
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Wang, Hongxin
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Shepherd, Nicholas E.
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Stokes, Philippa H.
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Blobel, Gerd A.
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Vermeulen, Michiel
fec6288a-88f4-4e35-beb0-22865bac5779
Glover, David M.
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Mackay, Joel P.
c0a1e4c8-76ce-47a9-a580-2270f27e3be7
Laue, Ernest D.
9bfea318-d6a1-493a-9055-41a9f9e06f17

Alqarni, Saad S.M., Murthy, Andal, Zhang, Wei, Przewloka, Marcin, Silva, Ana P.G., Watson, Aleksandra A., Lejon, Sara, Pei, Xue Y., Smits, Arne H., Kloet, Susan L., Wang, Hongxin, Shepherd, Nicholas E., Stokes, Philippa H., Blobel, Gerd A., Vermeulen, Michiel, Glover, David M., Mackay, Joel P. and Laue, Ernest D. (2014) Insight into the architecture of the NuRD complex: structure of the RbAp48-MTA1 subcomplex. The Journal of Biological Chemistry, 289 (32), 21844-21855. (doi:10.1074/jbc.M114.558940). (PMID:24920672)

Record type: Article

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.

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e-pub ahead of print date: 11 June 2014
Published date: 8 August 2014
Organisations: Molecular and Cellular, Centre for Biological Sciences

Identifiers

Local EPrints ID: 393858
URI: http://eprints.soton.ac.uk/id/eprint/393858
ISSN: 0021-9258
PURE UUID: 32974b1b-b480-4b61-a92c-6c12221c6f4c
ORCID for Marcin Przewloka: ORCID iD orcid.org/0000-0002-0329-9162

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Date deposited: 09 May 2016 09:22
Last modified: 17 Dec 2019 01:32

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