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

被引：59

作者：

Saini, Sunil Kumar ^{[1
]}

Mangalhara, Kailash Chandra ^{[1
]}

Prakasam, Gopinath ^{[1
]}

Bamezai, R. N. K. ^{[1
]}

机构：

[1] Jawaharlal Nehru Univ, Sch Life Sci, Natl Ctr Appl Human Genet, New Delhi 110067, India

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

ABSENCE; ORIGIN; MARKER; BREAST; MOUSE; CELLS;

D O I：

10.1038/s41598-017-01743-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

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