The structure of the core NuRD repression complex provides insights into its interaction with chromatin.
The NuRD complex is a multi-protein transcriptional corepressor that couples histone deacetylase and ATP-dependent chromatin remodelling activities. The complex regulates the higher-order structure of chromatin, and has important roles in the regulation of gene expression, DNA damage repair and cell differentiation. HDACs 1 and 2 are recruited by the MTA1 corepressor to form the catalytic core of the complex. The histone chaperone protein RBBP4, has previously been shown to bind to the carboxy-terminal tail of MTA1. We show that MTA1 recruits a second copy of RBBP4. The crystal structure reveals an extensive interface between MTA1 and RBBP4. An EM structure, supported by SAXS and crosslinking, reveals the architecture of the dimeric HDAC1:MTA1:RBBP4 assembly which forms the core of the NuRD complex. We find evidence that in this complex RBBP4 mediates interaction with histone H3 tails, but not histone H4, suggesting a mechanism for recruitment of the NuRD complex to chromatin.
Henry Wellcome Laboratories of Structural Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom.
Christopher J
http://orcid.org/0000-0002-1012-0829
CJ
Millard
Henry Wellcome Laboratories of Structural Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom.
Niranjan
N
Varma
Henry Wellcome Laboratories of Structural Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom.
Almutasem
http://orcid.org/0000-0002-0156-4508
A
Saleh
School of Life Sciences, University of Warwick, Coventry, United Kingdom.
Kyle
K
Morris
Henry Wellcome Laboratories of Structural Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom.
Peter J
PJ
Watson
Protein and Nucleic Acid Chemistry Laboratory, Core Biotechnology Services, University of Leicester, Leicester, United Kingdom.
Andrew R
http://orcid.org/0000-0002-5182-3643
AR
Bottrill
Henry Wellcome Laboratories of Structural Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom.
Louise
L
Fairall
School of Life Sciences, University of Warwick, Coventry, United Kingdom.
Corinne J
CJ
Smith
Henry Wellcome Laboratories of Structural Biology, Department of Molecular and Cell Biology, University of Leicester, Leicester, United Kingdom.
John W R
http://orcid.org/0000-0003-2865-4383
JW
Schwabe
D002843:Chromatin / Q000378:metabolism*; D018360:Crystallography, X-Ray; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000737:chemistry* / Q000378:metabolism*; D011487:Protein Conformation; D012097:Repressor Proteins; D056505:Retinoblastoma-Binding Protein 4; D015534:Trans-Activators
D002843:Chromatin; C089320:MTA1 protein, human; C082637:RBBP4 protein, human; D012097:Repressor Proteins; D056505:Retinoblastoma-Binding Protein 4; D015534:Trans-Activators; C110550:HDAC1 protein, human; C533423:HDAC2 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex
biochemistry; biophysics; chromatin; histone deacetylase; human; repression complex; structural biology; transcription regulation