Oxidative stress alters global histone modification and DNA methylation

The JmjC-domain-containing histone demethylases (JHDMs) can remove histone lysine-methylation and thereby regulate gene expression. The JmjC-domain uses iron Fe (II) and α-ketoglutarate (αKG) as cofactors in an oxidative demethylation reaction via hydroxymethyl-lysine. We hypothesize that reactive o...

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Main Authors:	Niu, Yingmei, DesMarais, Thomas L, Tong, Zhaohui, Yao, Yixin, Costa, Max
Format:	Online
Language:	English
Published:	2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464695/

id	pubmed-4464695
recordtype	oai_dc
spelling	pubmed-44646952016-05-01 Oxidative stress alters global histone modification and DNA methylation Niu, Yingmei DesMarais, Thomas L Tong, Zhaohui Yao, Yixin Costa, Max Article The JmjC-domain-containing histone demethylases (JHDMs) can remove histone lysine-methylation and thereby regulate gene expression. The JmjC-domain uses iron Fe (II) and α-ketoglutarate (αKG) as cofactors in an oxidative demethylation reaction via hydroxymethyl-lysine. We hypothesize that reactive oxygen species will oxidize Fe (II) to Fe (III), thereby attenuating the activity of JmjC-domain-containing histone demethylases. To minimize secondary responses from cells, extremely short periods of oxidative stress (3 hours) were used to investigate this question. Cells that were exposed to hydrogen peroxide (H2O2) for 3 hours, exhibited increases in several histone methylation marks including H3K4me3 and decreases of histone acetylation marks including H3K9ac and H4K8ac; pre-incubation with ascorbate attenuated these changes. The oxidative stress level was measured by generation of 2′, 7′-dichlorofluorescein (DCF), GSH/GSSG ratio and protein carbonyl content. A cell free system indicated H2O2 inhibited histone demethylase activity where increased Fe (II) rescued this inhibition. TET protein also showed a decreased activity under oxidative stress. Cells exposed to a low dose and long term (3 weeks) oxidative stress also showed increased global levels of H3K4me3 and H3K27me3. However, these global methylation changes did not persist after washout. The cells exposed to short term oxidative stress also appeared to have higher activity of class I/II histone deacetylase (HDAC) but not class III HDAC. In conclusion, we have found that oxidative stress transiently alters epigenetic program process through modulating the activity of enzymes responsible for demethylation and deacetylation of histones. 2015-02-03 2015-05 /pmc/articles/PMC4464695/ /pubmed/25656994 http://dx.doi.org/10.1016/j.freeradbiomed.2015.01.028 Text en © 2015 Published by Elsevier Inc. http://creativecommons.org/licenses/by/4.0/ This manuscript version is made available under the CC BY-NC-ND 4.0 license.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Niu, Yingmei DesMarais, Thomas L Tong, Zhaohui Yao, Yixin Costa, Max
spellingShingle	Niu, Yingmei DesMarais, Thomas L Tong, Zhaohui Yao, Yixin Costa, Max Oxidative stress alters global histone modification and DNA methylation
author_facet	Niu, Yingmei DesMarais, Thomas L Tong, Zhaohui Yao, Yixin Costa, Max
author_sort	Niu, Yingmei
title	Oxidative stress alters global histone modification and DNA methylation
title_short	Oxidative stress alters global histone modification and DNA methylation
title_full	Oxidative stress alters global histone modification and DNA methylation
title_fullStr	Oxidative stress alters global histone modification and DNA methylation
title_full_unstemmed	Oxidative stress alters global histone modification and DNA methylation
title_sort	oxidative stress alters global histone modification and dna methylation
description	The JmjC-domain-containing histone demethylases (JHDMs) can remove histone lysine-methylation and thereby regulate gene expression. The JmjC-domain uses iron Fe (II) and α-ketoglutarate (αKG) as cofactors in an oxidative demethylation reaction via hydroxymethyl-lysine. We hypothesize that reactive oxygen species will oxidize Fe (II) to Fe (III), thereby attenuating the activity of JmjC-domain-containing histone demethylases. To minimize secondary responses from cells, extremely short periods of oxidative stress (3 hours) were used to investigate this question. Cells that were exposed to hydrogen peroxide (H2O2) for 3 hours, exhibited increases in several histone methylation marks including H3K4me3 and decreases of histone acetylation marks including H3K9ac and H4K8ac; pre-incubation with ascorbate attenuated these changes. The oxidative stress level was measured by generation of 2′, 7′-dichlorofluorescein (DCF), GSH/GSSG ratio and protein carbonyl content. A cell free system indicated H2O2 inhibited histone demethylase activity where increased Fe (II) rescued this inhibition. TET protein also showed a decreased activity under oxidative stress. Cells exposed to a low dose and long term (3 weeks) oxidative stress also showed increased global levels of H3K4me3 and H3K27me3. However, these global methylation changes did not persist after washout. The cells exposed to short term oxidative stress also appeared to have higher activity of class I/II histone deacetylase (HDAC) but not class III HDAC. In conclusion, we have found that oxidative stress transiently alters epigenetic program process through modulating the activity of enzymes responsible for demethylation and deacetylation of histones.
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464695/
_version_	1613234902821502976

Oxidative stress alters global histone modification and DNA methylation

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