Kelly, R.D.W., Chandru, A., Watson, P.J., Song, Y., Blades, M., Robertson, N.S., Jamieson, A.G. , Schwabe, J.W.R. and Cowley, S.M. (2018) Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo. Scientific Reports, 8, 14690. (doi: 10.1038/s41598-018-32927-9) (PMID:30279482) (PMCID:PMC6168483)
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Abstract
Proteomic analysis of histones has shown that they are subject to a superabundance of acylations, which extend far beyond acetylation, to include: crotonylation, propionylation, butyrylation, malonylation, succinylation, β-hydroxybutyrylation and 2-hydroxyisobutyrylation. To date, much of the functional data has focussed on histone crotonylation which, similar to acetylation, has been associated with positive gene regulation and is added by the acyltransferase, p300. Although Sirtuins 1-3, along with HDAC3, have been shown to possess decrotonylase activity in vitro, there is relatively little known about the regulation of histone crotonylation in vivo. Here we show that Histone Deacetylase 1 and 2 (HDAC1/2), the catalytic core of numerous co-repressor complexes, are important histone decrotonylase enzymes. A ternary complex of HDAC1/CoREST1/LSD1 is able to hydrolyse both histone H3 Lys18-acetyl (H3K18ac) and H3 Lys18-crotonyl (H3K18cr) peptide substrates. Genetic deletion of HDAC1/2 in ES cells increases global levels of histone crotonylation and causes an 85% reduction in total decrotonylase activity. Furthermore, we mapped H3K18cr in cells using ChIP-seq, with and without HDAC1/2, and observed increased levels of crotonylation, which largely overlaps with H3K18ac in the vicinity of transcriptional start sites. Collectively, our data indicate that HDAC1/2 containing complexes are critical regulators of histone crotonylation in vivo.
| Item Type: | Articles |
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| Additional Information: | JWRS was supported by grants from the BBSRC (BB/N002954/1) and Wellcome Trust (100237). SMC was supported by a senior non-clinical fellowship from the MRC (MR/J009202/1) and BBSRC project grants (BB/N002954/1, BB/P021689/1). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Jamieson, Professor Andrew |
| Authors: | Kelly, R.D.W., Chandru, A., Watson, P.J., Song, Y., Blades, M., Robertson, N.S., Jamieson, A.G., Schwabe, J.W.R., and Cowley, S.M. |
| College/School: | College of Science and Engineering > School of Chemistry |
| Journal Name: | Scientific Reports |
| Publisher: | Nature Research |
| ISSN: | 2045-2322 |
| ISSN (Online): | 2045-2322 |
| Copyright Holders: | Copyright © 2018 The Authors |
| First Published: | First published in Scientific Reports 8(1):14690 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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