Cargando…

Vascular histone deacetylation by pharmacological HDAC inhibition

HDAC inhibitors can regulate gene expression by post-translational modification of histone as well as nonhistone proteins. Often studied at single loci, increased histone acetylation is the paradigmatic mechanism of action. However, little is known of the extent of genome-wide changes in cells stimu...

Descripción completa

Detalles Bibliográficos
Autores principales: Rafehi, Haloom, Balcerczyk, Aneta, Lunke, Sebastian, Kaspi, Antony, Ziemann, Mark, KN, Harikrishnan, Okabe, Jun, Khurana, Ishant, Ooi, Jenny, Khan, Abdul Waheed, Du, Xiao-Jun, Chang, Lisa, Haviv, Izhak, Keating, Samuel T., Karagiannis, Tom C., El-Osta, Assam
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120081/
https://www.ncbi.nlm.nih.gov/pubmed/24732587
http://dx.doi.org/10.1101/gr.168781.113
_version_ 1782329037691027456
author Rafehi, Haloom
Balcerczyk, Aneta
Lunke, Sebastian
Kaspi, Antony
Ziemann, Mark
KN, Harikrishnan
Okabe, Jun
Khurana, Ishant
Ooi, Jenny
Khan, Abdul Waheed
Du, Xiao-Jun
Chang, Lisa
Haviv, Izhak
Keating, Samuel T.
Karagiannis, Tom C.
El-Osta, Assam
author_facet Rafehi, Haloom
Balcerczyk, Aneta
Lunke, Sebastian
Kaspi, Antony
Ziemann, Mark
KN, Harikrishnan
Okabe, Jun
Khurana, Ishant
Ooi, Jenny
Khan, Abdul Waheed
Du, Xiao-Jun
Chang, Lisa
Haviv, Izhak
Keating, Samuel T.
Karagiannis, Tom C.
El-Osta, Assam
author_sort Rafehi, Haloom
collection PubMed
description HDAC inhibitors can regulate gene expression by post-translational modification of histone as well as nonhistone proteins. Often studied at single loci, increased histone acetylation is the paradigmatic mechanism of action. However, little is known of the extent of genome-wide changes in cells stimulated by the hydroxamic acids, TSA and SAHA. In this article, we map vascular chromatin modifications including histone H3 acetylation of lysine 9 and 14 (H3K9/14ac) using chromatin immunoprecipitation (ChIP) coupled with massive parallel sequencing (ChIP-seq). Since acetylation-mediated gene expression is often associated with modification of other lysine residues, we also examined H3K4me3 and H3K9me3 as well as changes in CpG methylation (CpG-seq). RNA sequencing indicates the differential expression of ∼30% of genes, with almost equal numbers being up- and down-regulated. We observed broad deacetylation and gene expression changes conferred by TSA and SAHA mediated by the loss of EP300/CREBBP binding at multiple gene promoters. This study provides an important framework for HDAC inhibitor function in vascular biology and a comprehensive description of genome-wide deacetylation by pharmacological HDAC inhibition.
format Online
Article
Text
id pubmed-4120081
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-41200812015-02-01 Vascular histone deacetylation by pharmacological HDAC inhibition Rafehi, Haloom Balcerczyk, Aneta Lunke, Sebastian Kaspi, Antony Ziemann, Mark KN, Harikrishnan Okabe, Jun Khurana, Ishant Ooi, Jenny Khan, Abdul Waheed Du, Xiao-Jun Chang, Lisa Haviv, Izhak Keating, Samuel T. Karagiannis, Tom C. El-Osta, Assam Genome Res Research HDAC inhibitors can regulate gene expression by post-translational modification of histone as well as nonhistone proteins. Often studied at single loci, increased histone acetylation is the paradigmatic mechanism of action. However, little is known of the extent of genome-wide changes in cells stimulated by the hydroxamic acids, TSA and SAHA. In this article, we map vascular chromatin modifications including histone H3 acetylation of lysine 9 and 14 (H3K9/14ac) using chromatin immunoprecipitation (ChIP) coupled with massive parallel sequencing (ChIP-seq). Since acetylation-mediated gene expression is often associated with modification of other lysine residues, we also examined H3K4me3 and H3K9me3 as well as changes in CpG methylation (CpG-seq). RNA sequencing indicates the differential expression of ∼30% of genes, with almost equal numbers being up- and down-regulated. We observed broad deacetylation and gene expression changes conferred by TSA and SAHA mediated by the loss of EP300/CREBBP binding at multiple gene promoters. This study provides an important framework for HDAC inhibitor function in vascular biology and a comprehensive description of genome-wide deacetylation by pharmacological HDAC inhibition. Cold Spring Harbor Laboratory Press 2014-08 /pmc/articles/PMC4120081/ /pubmed/24732587 http://dx.doi.org/10.1101/gr.168781.113 Text en © 2014 Rafehi et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
Rafehi, Haloom
Balcerczyk, Aneta
Lunke, Sebastian
Kaspi, Antony
Ziemann, Mark
KN, Harikrishnan
Okabe, Jun
Khurana, Ishant
Ooi, Jenny
Khan, Abdul Waheed
Du, Xiao-Jun
Chang, Lisa
Haviv, Izhak
Keating, Samuel T.
Karagiannis, Tom C.
El-Osta, Assam
Vascular histone deacetylation by pharmacological HDAC inhibition
title Vascular histone deacetylation by pharmacological HDAC inhibition
title_full Vascular histone deacetylation by pharmacological HDAC inhibition
title_fullStr Vascular histone deacetylation by pharmacological HDAC inhibition
title_full_unstemmed Vascular histone deacetylation by pharmacological HDAC inhibition
title_short Vascular histone deacetylation by pharmacological HDAC inhibition
title_sort vascular histone deacetylation by pharmacological hdac inhibition
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4120081/
https://www.ncbi.nlm.nih.gov/pubmed/24732587
http://dx.doi.org/10.1101/gr.168781.113
work_keys_str_mv AT rafehihaloom vascularhistonedeacetylationbypharmacologicalhdacinhibition
AT balcerczykaneta vascularhistonedeacetylationbypharmacologicalhdacinhibition
AT lunkesebastian vascularhistonedeacetylationbypharmacologicalhdacinhibition
AT kaspiantony vascularhistonedeacetylationbypharmacologicalhdacinhibition
AT ziemannmark vascularhistonedeacetylationbypharmacologicalhdacinhibition
AT knharikrishnan vascularhistonedeacetylationbypharmacologicalhdacinhibition
AT okabejun vascularhistonedeacetylationbypharmacologicalhdacinhibition
AT khuranaishant vascularhistonedeacetylationbypharmacologicalhdacinhibition
AT ooijenny vascularhistonedeacetylationbypharmacologicalhdacinhibition
AT khanabdulwaheed vascularhistonedeacetylationbypharmacologicalhdacinhibition
AT duxiaojun vascularhistonedeacetylationbypharmacologicalhdacinhibition
AT changlisa vascularhistonedeacetylationbypharmacologicalhdacinhibition
AT havivizhak vascularhistonedeacetylationbypharmacologicalhdacinhibition
AT keatingsamuelt vascularhistonedeacetylationbypharmacologicalhdacinhibition
AT karagiannistomc vascularhistonedeacetylationbypharmacologicalhdacinhibition
AT elostaassam vascularhistonedeacetylationbypharmacologicalhdacinhibition