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Diverse nucleosome Site-Selectivity among histone deacetylase complexes

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-selectiviti...

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Autores principales: Wang, Zhipeng A, Millard, Christopher J, Lin, Chia-Liang, Gurnett, Jennifer E, Wu, Mingxuan, Lee, Kwangwoon, Fairall, Louise, Schwabe, John WR, Cole, Philip A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316510/
https://www.ncbi.nlm.nih.gov/pubmed/32501215
http://dx.doi.org/10.7554/eLife.57663
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author Wang, Zhipeng A
Millard, Christopher J
Lin, Chia-Liang
Gurnett, Jennifer E
Wu, Mingxuan
Lee, Kwangwoon
Fairall, Louise
Schwabe, John WR
Cole, Philip A
author_facet Wang, Zhipeng A
Millard, Christopher J
Lin, Chia-Liang
Gurnett, Jennifer E
Wu, Mingxuan
Lee, Kwangwoon
Fairall, Louise
Schwabe, John WR
Cole, Philip A
author_sort Wang, Zhipeng A
collection PubMed
description 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 (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.
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spelling pubmed-73165102020-06-29 Diverse nucleosome Site-Selectivity among histone deacetylase complexes Wang, Zhipeng A Millard, Christopher J Lin, Chia-Liang Gurnett, Jennifer E Wu, Mingxuan Lee, Kwangwoon Fairall, Louise Schwabe, John WR Cole, Philip A eLife Biochemistry and Chemical Biology 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 (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. eLife Sciences Publications, Ltd 2020-06-05 /pmc/articles/PMC7316510/ /pubmed/32501215 http://dx.doi.org/10.7554/eLife.57663 Text en © 2020, Wang et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry and Chemical Biology
Wang, Zhipeng A
Millard, Christopher J
Lin, Chia-Liang
Gurnett, Jennifer E
Wu, Mingxuan
Lee, Kwangwoon
Fairall, Louise
Schwabe, John WR
Cole, Philip A
Diverse nucleosome Site-Selectivity among histone deacetylase complexes
title Diverse nucleosome Site-Selectivity among histone deacetylase complexes
title_full Diverse nucleosome Site-Selectivity among histone deacetylase complexes
title_fullStr Diverse nucleosome Site-Selectivity among histone deacetylase complexes
title_full_unstemmed Diverse nucleosome Site-Selectivity among histone deacetylase complexes
title_short Diverse nucleosome Site-Selectivity among histone deacetylase complexes
title_sort diverse nucleosome site-selectivity among histone deacetylase complexes
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316510/
https://www.ncbi.nlm.nih.gov/pubmed/32501215
http://dx.doi.org/10.7554/eLife.57663
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