DNA Methyltransferase1 (DNMT1) Isoform3 methylates mitochondrial genome and modulates its biology

Abstract Here we demonstrate localization of the isoform3 of DNA Methyltransferase1 (DNMT1) enzyme to mitochondria, instead of isoform1 as reported earlier. The fused DNMT1-isoform1, reported earlier to localize in mitochondria, surprisingly showed its exclusive presence inside the nucleus after its...

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Autores principales:	Sunil Kumar Saini, Kailash Chandra Mangalhara, Gopinath Prakasam, R. N. K. Bamezai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/05a5af99ff31489f98ba8f2624253fd6
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spelling	oai:doaj.org-article:05a5af99ff31489f98ba8f2624253fd62021-12-02T11:53:12ZDNA Methyltransferase1 (DNMT1) Isoform3 methylates mitochondrial genome and modulates its biology10.1038/s41598-017-01743-y2045-2322https://doaj.org/article/05a5af99ff31489f98ba8f2624253fd62017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01743-yhttps://doaj.org/toc/2045-2322Abstract Here we demonstrate localization of the isoform3 of DNA Methyltransferase1 (DNMT1) enzyme to mitochondria, instead of isoform1 as reported earlier. The fused DNMT1-isoform1, reported earlier to localize in mitochondria, surprisingly showed its exclusive presence inside the nucleus after its ectopic expression; and failed to localize in mitochondria. On the other hand, ectopically expressed DNMT1-isoform3 targeted itself to mitochondria and subsequently methylated CpG regions in the mitochondrial genome. In addition, overexpression of DNMT1-isoform3 affected mitochondrial biology and regulated its function. Under different conditions of oxidative and nutritional stress, this isoform was down-regulated, resulting in hypomethylation of mitochondrial genome. Our study reveals how DNMT1-isoform3, instead of isoform1, is responsible for mtDNA methylation, influencing its biology.Sunil Kumar SainiKailash Chandra MangalharaGopinath PrakasamR. N. K. BamezaiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sunil Kumar Saini Kailash Chandra Mangalhara Gopinath Prakasam R. N. K. Bamezai DNA Methyltransferase1 (DNMT1) Isoform3 methylates mitochondrial genome and modulates its biology
description	Abstract Here we demonstrate localization of the isoform3 of DNA Methyltransferase1 (DNMT1) enzyme to mitochondria, instead of isoform1 as reported earlier. The fused DNMT1-isoform1, reported earlier to localize in mitochondria, surprisingly showed its exclusive presence inside the nucleus after its ectopic expression; and failed to localize in mitochondria. On the other hand, ectopically expressed DNMT1-isoform3 targeted itself to mitochondria and subsequently methylated CpG regions in the mitochondrial genome. In addition, overexpression of DNMT1-isoform3 affected mitochondrial biology and regulated its function. Under different conditions of oxidative and nutritional stress, this isoform was down-regulated, resulting in hypomethylation of mitochondrial genome. Our study reveals how DNMT1-isoform3, instead of isoform1, is responsible for mtDNA methylation, influencing its biology.
format	article
author	Sunil Kumar Saini Kailash Chandra Mangalhara Gopinath Prakasam R. N. K. Bamezai
author_facet	Sunil Kumar Saini Kailash Chandra Mangalhara Gopinath Prakasam R. N. K. Bamezai
author_sort	Sunil Kumar Saini
title	DNA Methyltransferase1 (DNMT1) Isoform3 methylates mitochondrial genome and modulates its biology
title_short	DNA Methyltransferase1 (DNMT1) Isoform3 methylates mitochondrial genome and modulates its biology
title_full	DNA Methyltransferase1 (DNMT1) Isoform3 methylates mitochondrial genome and modulates its biology
title_fullStr	DNA Methyltransferase1 (DNMT1) Isoform3 methylates mitochondrial genome and modulates its biology
title_full_unstemmed	DNA Methyltransferase1 (DNMT1) Isoform3 methylates mitochondrial genome and modulates its biology
title_sort	dna methyltransferase1 (dnmt1) isoform3 methylates mitochondrial genome and modulates its biology
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/05a5af99ff31489f98ba8f2624253fd6
work_keys_str_mv	AT sunilkumarsaini dnamethyltransferase1dnmt1isoform3methylatesmitochondrialgenomeandmodulatesitsbiology AT kailashchandramangalhara dnamethyltransferase1dnmt1isoform3methylatesmitochondrialgenomeandmodulatesitsbiology AT gopinathprakasam dnamethyltransferase1dnmt1isoform3methylatesmitochondrialgenomeandmodulatesitsbiology AT rnkbamezai dnamethyltransferase1dnmt1isoform3methylatesmitochondrialgenomeandmodulatesitsbiology
_version_	1718394847206834176

DNA Methyltransferase1 (DNMT1) Isoform3 methylates mitochondrial genome and modulates its biology

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