Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression

Abstract Like the nucleus, mitochondria contain their own DNA and recent reports provide accumulating evidence that also the mitochondrial DNA (mtDNA) is subjective to DNA methylation. This evidence includes the demonstration of mitochondria-localised DNA methyltransferases and demethylases, and the...

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Autores principales:	Monique G. P. van der Wijst, Amanda Y. van Tilburg, Marcel H. J. Ruiters, Marianne G. Rots
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/25dc5d0acc3d498d832bc3739fe8b849
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spelling	oai:doaj.org-article:25dc5d0acc3d498d832bc3739fe8b8492021-12-02T16:08:22ZExperimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression10.1038/s41598-017-00263-z2045-2322https://doaj.org/article/25dc5d0acc3d498d832bc3739fe8b8492017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00263-zhttps://doaj.org/toc/2045-2322Abstract Like the nucleus, mitochondria contain their own DNA and recent reports provide accumulating evidence that also the mitochondrial DNA (mtDNA) is subjective to DNA methylation. This evidence includes the demonstration of mitochondria-localised DNA methyltransferases and demethylases, and the detection of mtDNA methylation as well as hydroxymethylation. Importantly, differential mtDNA methylation has been linked to aging and diseases, including cancer and diabetes. However, functionality of mtDNA methylation has not been demonstrated. Therefore, we targeted DNA methylating enzymes (modifying cytosine in the CpG or GpC context) to the mtDNA. Unexpectedly, mtDNA gene expression remained unchanged upon induction of CpG mtDNA methylation, whereas induction of C-methylation in the GpC context decreased mtDNA gene expression. Intriguingly, in the latter case, the three mtDNA promoters were differentially affected in each cell line, while cellular function seemed undisturbed. In conclusion, this is the first study which directly addresses the potential functionality of mtDNA methylation. Giving the important role of mitochondria in health and disease, unravelling the impact of mtDNA methylation adds to our understanding of the role of mitochondria in physiological and pathophysiological processes.Monique G. P. van der WijstAmanda Y. van TilburgMarcel H. J. RuitersMarianne G. RotsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Monique G. P. van der Wijst Amanda Y. van Tilburg Marcel H. J. Ruiters Marianne G. Rots Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression
description	Abstract Like the nucleus, mitochondria contain their own DNA and recent reports provide accumulating evidence that also the mitochondrial DNA (mtDNA) is subjective to DNA methylation. This evidence includes the demonstration of mitochondria-localised DNA methyltransferases and demethylases, and the detection of mtDNA methylation as well as hydroxymethylation. Importantly, differential mtDNA methylation has been linked to aging and diseases, including cancer and diabetes. However, functionality of mtDNA methylation has not been demonstrated. Therefore, we targeted DNA methylating enzymes (modifying cytosine in the CpG or GpC context) to the mtDNA. Unexpectedly, mtDNA gene expression remained unchanged upon induction of CpG mtDNA methylation, whereas induction of C-methylation in the GpC context decreased mtDNA gene expression. Intriguingly, in the latter case, the three mtDNA promoters were differentially affected in each cell line, while cellular function seemed undisturbed. In conclusion, this is the first study which directly addresses the potential functionality of mtDNA methylation. Giving the important role of mitochondria in health and disease, unravelling the impact of mtDNA methylation adds to our understanding of the role of mitochondria in physiological and pathophysiological processes.
format	article
author	Monique G. P. van der Wijst Amanda Y. van Tilburg Marcel H. J. Ruiters Marianne G. Rots
author_facet	Monique G. P. van der Wijst Amanda Y. van Tilburg Marcel H. J. Ruiters Marianne G. Rots
author_sort	Monique G. P. van der Wijst
title	Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression
title_short	Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression
title_full	Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression
title_fullStr	Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression
title_full_unstemmed	Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression
title_sort	experimental mitochondria-targeted dna methylation identifies gpc methylation, not cpg methylation, as potential regulator of mitochondrial gene expression
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/25dc5d0acc3d498d832bc3739fe8b849
work_keys_str_mv	AT moniquegpvanderwijst experimentalmitochondriatargeteddnamethylationidentifiesgpcmethylationnotcpgmethylationaspotentialregulatorofmitochondrialgeneexpression AT amandayvantilburg experimentalmitochondriatargeteddnamethylationidentifiesgpcmethylationnotcpgmethylationaspotentialregulatorofmitochondrialgeneexpression AT marcelhjruiters experimentalmitochondriatargeteddnamethylationidentifiesgpcmethylationnotcpgmethylationaspotentialregulatorofmitochondrialgeneexpression AT mariannegrots experimentalmitochondriatargeteddnamethylationidentifiesgpcmethylationnotcpgmethylationaspotentialregulatorofmitochondrialgeneexpression
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Experimental mitochondria-targeted DNA methylation identifies GpC methylation, not CpG methylation, as potential regulator of mitochondrial gene expression

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