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

Hudson, G. M., Watson, P. J., Fairall, L., Jamieson, A. G. and Schwabe, J. W.R. (2015) Insights into the recruitment of class IIa Histone Deacetylases (HDACs) to the SMRT/NCoR transcriptional repression complex. Journal of Biological Chemistry, 290(29), pp. 18237-18244. (doi: 10.1074/jbc.M115.661058) (PMID:26055705) (PMCID:PMC4505066)

Abstract

Class IIa histone deacetylases repress transcription of target genes. However, their mechanism of action is poorly understood because they exhibit very low levels of deacetylase activity. The class IIa HDACs are associated with the SMRT/NCoR repression complexes and this may, at least in part, account 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, and 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.

• Item Type: Articles
• Additional Information: This work was supported in part by Wellcome Trust Programme and Senior Investigator Awards WT085408 and WT100237.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Jamieson, Professor Andrew
• Authors: Hudson, G. M., Watson, P. J., Fairall, L., Jamieson, A. G., and Schwabe, J. W.R.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Journal of Biological Chemistry
• Publisher: American Society for Biochemistry and Molecular Biology
• ISSN: 0021-9258
• ISSN (Online): 1083-351X
• Published Online: 08 July 2015
• Copyright Holders: Copyright © 2015 The Authors
• First Published: First published in Journal of Biological Chemistry 290(29):18237-18244
• Publisher Policy: Reproduced under a creative commons license