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Insights into the recruitment of class IIa Histone Deacetylases (HDACs) to the SMRT/NCoR transcriptional repression complex

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journal contribution
posted on 08.06.2015, 14:47 by Gregg M. Hudson, Peter J. Watson, Louise Fairall, Andrew G. Jamieson, John W. R. Schwabe
Class IIa histone deacetylases repress transcription of target genes. However their mechanism of action is poorly understood since they exhibit very low levels of deacetylase activity. The class IIa HDACs are associated with the SMRT / NCoR re pression complexes and this may, at least in part, a ccount for their repressive activity. However, the molecular mechanism of recruitment to co - repressor proteins has yet to be established. Here we show that a repeated peptide motif present in both SMRT and NCoR is sufficient to mediate specific interaction , with micromolar affinity, with all the class IIa HDACs (HDACs 4, 5, 7 & 9). Mutations in the consensus motif abrogate binding. Mutational analysis of HDAC4 suggests that the peptide interacts in the vicinity of the active site of the enzyme and requires the “closed” conformation of the zinc - binding loop on the surface of the enzyme. Together these findings represent the first insights into the molecular mechanism of recruitment of class IIa HDACs to the SMRT / NCoR repression complexes.

Funding

This work was supported in part by Wellcome Trust Programme and Senior Investigator Awards WT085408 and WT100237.

History

Citation

Journal of Biological Chemistry, 2015 290, 18237-18244.

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Biological Sciences/Department of Biochemistry

Version

VoR (Version of Record)

Published in

Journal of Biological Chemistry

Publisher

American Society for Biochemistry and Molecular Biology

issn

0021-9258;1083-351X

Copyright date

2015

Available date

20/08/2015

Publisher version

http://www.jbc.org/content/290/29/18237.short

Language

en

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