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Title: Class I HDACs share a common mechanism of regulation by inositol phosphates.
Authors: Millard, Christopher J.
Watson, Peter J.
Celardo, Ivana
Gordiyenko, Y.
Cowley, Shaun M.
Robinson, C. V.
Fairall, Louise
Schwabe, John W. R.
First Published: 20-Jun-2013
Publisher: Elsevier (Cell Press)
Citation: Molecular Cell, 2013, 51 (1), pp. 57-67
Abstract: Class I histone deacetylases (HDAC1, HDAC2, and HDAC3) are recruited by cognate corepressor proteins into specific transcriptional repression complexes that target HDAC activity to chromatin resulting in chromatin condensation and transcriptional silencing. We previously reported the structure of HDAC3 in complex with the SMRT corepressor. This structure revealed the presence of inositol-tetraphosphate [Ins(1,4,5,6)P4] at the interface of the two proteins. It was previously unclear whether the role of Ins(1,4,5,6)P4 is to act as a structural cofactor or a regulator of HDAC3 activity. Here we report the structure of HDAC1 in complex with MTA1 from the NuRD complex. The ELM2-SANT domains from MTA1 wrap completely around HDAC1 occupying both sides of the active site such that the adjacent BAH domain is ideally positioned to recruit nucleosomes to the active site of the enzyme. Functional assays of both the HDAC1 and HDAC3 complexes reveal that Ins(1,4,5,6)P4 is a bona fide conserved regulator of class I HDAC complexes.
DOI Link: 10.1016/j.molcel.2013.05.020
ISSN: 1097-2765
eISSN: 1097-4164
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Open access under CC BY-NC-ND license.
Description: PMCID: PMC3710971 The coordinates and structure factors for the HDAC1:MTA1 complex crystal structure reported in this paper have been deposited in the Protein Data Bank under accession code 4bkx.
Appears in Collections:Published Articles, Dept. of Biochemistry

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