Diverse nucleosome site-selectivity among histone deacetylase complexes
- Brigham and Women's Hospital, United States
- University of Leicester, United Kingdom
- Harvard Medical School, United States
Abstract
Histone acetylation regulates chromatin structure and gene expression and is removed by histone deacetylases (HDACs). HDACs are commonly found in various protein complexes to confer distinct cellular functions, but how the multi-subunit complexes influence deacetylase activities and site-selectivities in chromatin is poorly understood. Previously we reported the results of studies on the HDAC1 containing CoREST complex and acetylated nucleosome substrates which revealed a notable preference for deacetylation of histone H3 acetyl-Lys9 vs. acetyl-Lys14 (M. Wu et al, 2018). Here we analyze the enzymatic properties of five class I HDAC complexes: CoREST, NuRD, Sin3B, MiDAC and SMRT with site-specific acetylated nucleosome substrates. Our results demonstrate that these HDAC complexes show a wide variety of deacetylase rates in a site-selective manner. A Gly13 in the histone H3 tail is responsible for a sharp reduction in deacetylase activity of the CoREST complex for H3K14ac. These studies provide a framework for connecting enzymatic and biological functions of specific HDAC complexes.
Data availability
Data has been uploaded to Dryad under the doi:10.5061/dryad.x0k6djhgc
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Diverse nucleosome site-selectivity among histone deacetylase complexesDryad Digital Repository, doi:10.5061/dryad.x0k6djhgc.
Article and author information
Author details
Funding
NIH (GM62437)
- Philip A Cole
Leukemia and Lymphoma Society (SCOR)
- Philip A Cole
Wellcome Trust Senior Investigator Award (100237/Z/12/Z)
- John W R Schwabe
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Diverse nucleosome site-selectivity among histone deacetylase complexes
eLife 9:e57663.
https://doi.org/10.7554/eLife.57663
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