Activation of p21 by HDAC inhibitors requires acetylation of H2A.Z.

Differential positioning of the histone variant H2A.Z in a p53 dependent manner was shown to regulate p21 transcription. Whether H2A.Z is involved in p21 activity in the absence of p53 is not known. The p21 gene is repressed in estrogen receptor (ER) negative cell lines that are p53-/- and hormone i...

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Autores principales:	Luca Bellucci, Mathieu Dalvai, Silvia Kocanova, Fatima Moutahir, Kerstin Bystricky
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c0ab82d03589495dbb95fd7f58f859e3
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spelling	oai:doaj.org-article:c0ab82d03589495dbb95fd7f58f859e32021-11-18T08:00:53ZActivation of p21 by HDAC inhibitors requires acetylation of H2A.Z.1932-620310.1371/journal.pone.0054102https://doaj.org/article/c0ab82d03589495dbb95fd7f58f859e32013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23349794/?tool=EBIhttps://doaj.org/toc/1932-6203Differential positioning of the histone variant H2A.Z in a p53 dependent manner was shown to regulate p21 transcription. Whether H2A.Z is involved in p21 activity in the absence of p53 is not known. The p21 gene is repressed in estrogen receptor (ER) negative cell lines that are p53-/- and hormone independent for their growth. Here we demonstrate that class I and II pan Histone deacetylase inhibitors (HDACi) induce p21 transcription and reduce cell proliferation of MDA-MB231, an ERα-negative mammary tumor cell line, in a H2A.Z dependent manner. H2A.Z is associated with the transcription start site (TSS) of the repressed p21 gene. Depleting H2A.Z did not lead to transcription of p21 but annihilated the stimulating effect of HDACi on this gene. Acetylation of H2A.Z but not of H3K9 at the p21 promoter correlated with p21 activation. We further show that HDACi treatment reduced the presence of the p400 chromatin remodeler at the p21 TSS. We propose a model in which association of p400 negatively affects p21 transcription by interfering with acetylation of H2A.Z.Luca BellucciMathieu DalvaiSilvia KocanovaFatima MoutahirKerstin BystrickyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e54102 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Luca Bellucci Mathieu Dalvai Silvia Kocanova Fatima Moutahir Kerstin Bystricky Activation of p21 by HDAC inhibitors requires acetylation of H2A.Z.
description	Differential positioning of the histone variant H2A.Z in a p53 dependent manner was shown to regulate p21 transcription. Whether H2A.Z is involved in p21 activity in the absence of p53 is not known. The p21 gene is repressed in estrogen receptor (ER) negative cell lines that are p53-/- and hormone independent for their growth. Here we demonstrate that class I and II pan Histone deacetylase inhibitors (HDACi) induce p21 transcription and reduce cell proliferation of MDA-MB231, an ERα-negative mammary tumor cell line, in a H2A.Z dependent manner. H2A.Z is associated with the transcription start site (TSS) of the repressed p21 gene. Depleting H2A.Z did not lead to transcription of p21 but annihilated the stimulating effect of HDACi on this gene. Acetylation of H2A.Z but not of H3K9 at the p21 promoter correlated with p21 activation. We further show that HDACi treatment reduced the presence of the p400 chromatin remodeler at the p21 TSS. We propose a model in which association of p400 negatively affects p21 transcription by interfering with acetylation of H2A.Z.
format	article
author	Luca Bellucci Mathieu Dalvai Silvia Kocanova Fatima Moutahir Kerstin Bystricky
author_facet	Luca Bellucci Mathieu Dalvai Silvia Kocanova Fatima Moutahir Kerstin Bystricky
author_sort	Luca Bellucci
title	Activation of p21 by HDAC inhibitors requires acetylation of H2A.Z.
title_short	Activation of p21 by HDAC inhibitors requires acetylation of H2A.Z.
title_full	Activation of p21 by HDAC inhibitors requires acetylation of H2A.Z.
title_fullStr	Activation of p21 by HDAC inhibitors requires acetylation of H2A.Z.
title_full_unstemmed	Activation of p21 by HDAC inhibitors requires acetylation of H2A.Z.
title_sort	activation of p21 by hdac inhibitors requires acetylation of h2a.z.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c0ab82d03589495dbb95fd7f58f859e3
work_keys_str_mv	AT lucabellucci activationofp21byhdacinhibitorsrequiresacetylationofh2az AT mathieudalvai activationofp21byhdacinhibitorsrequiresacetylationofh2az AT silviakocanova activationofp21byhdacinhibitorsrequiresacetylationofh2az AT fatimamoutahir activationofp21byhdacinhibitorsrequiresacetylationofh2az AT kerstinbystricky activationofp21byhdacinhibitorsrequiresacetylationofh2az
_version_	1718422693464768512

Activation of p21 by HDAC inhibitors requires acetylation of H2A.Z.

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