The strand-biased mitochondrial DNA methylome and its regulation by DNMT3A

被引：58

作者：

Dou, Xiaoyang ^{[1
,2
]}

Boyd-Kirkup, Jerome D. ^{[1
]}

McDermott, Joseph ^{[1
]}

Zhang, Xiaoli ^{[1
,3
]}

Li, Fang ^{[1
]}

Rong, Bowen ^{[4
,5
]}

Zhang, Rui ^{[1
]}

Miao, Bisi ^{[4
,5
]}

Chen, Peilin ^{[6
,7
]}

Cheng, Hao ^{[1
]}

Xue, Jianhuang ^{[8
]}

Bennett, David ^{[9
]}

Wong, Jiemin ^{[6
,7
]}

Lan, Fei ^{[4
,5
]}

Han, Jing-Dong J. ^{[1
,3
]}

机构：

[1] Chinese Acad Sci, Collaborat Innovat Ctr Genet & Dev Biol, Max Planck Partner Inst Computat Biol,CAS Ctr Exc, Shanghai Inst Biol Sci,Key Lab Computat Biol, Shanghai 200031, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[3] Peking Univ, CQB, Acad Adv Interdisciplinary Studies, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China

[4] Fudan Univ, Key Lab Carcinogenesis & Canc Invas, Zhongshan Hosp,LiverCanc Inst, Minist Educ,Shanghai Minist Educ,Key Lab Epigenet, Shanghai 200032, Peoples R China

[5] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China

[6] East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai 200241, Peoples R China

[7] East China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China

[8] Chinese Acad Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai 200031, Peoples R China

[9] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA

来源：

GENOME RESEARCH | 2019年 / 29卷 / 10期

基金：

美国国家科学基金会; 中国国家自然科学基金;

关键词：

EPIGENETIC REGULATION; CPG METHYLATION; SELF-RENEWAL; MOUSE; GENOME; ABSENCE; CELLS; 5-HYDROXYMETHYLCYTOSINE; SHOWS; WIDE;

D O I：

10.1101/gr.234021.117

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

How individual genes are regulated from a mitochondrial polycistronic transcript to have variable expression remains an enigma. Here, through bisulfite sequencing and strand-specific mapping, we show mitochondrial genomes in humans and other animals are strongly biased to light (L)-strand non-CpG methylation with conserved peak loci preferentially located at gene-gene boundaries, which was also independently validated by MeDIP and FspEl digestion. Such mtDNA methylation patterns are conserved across different species and developmental stages but display dynamic local or global changes during development and aging. Knockout of DNMT3A alone perturbed mtDNA regional methylation patterns, but not global levels, and altered mitochondrial gene expression, copy number, and oxygen respiration. Overexpression of DNMT3A strongly increased mtDNA methylation and strand bias. Overall, methylation at gene bodies and boundaries was negatively associated with mitochondrial transcript abundance and also polycistronic transcript processing. Furthermore, HPLC-MS confirmed the methylation signals on mitochondria DNA. Together, these data provide high-resolution mtDNA methylation maps that revealed a strand-specific non-CpG methylation, its dynamic regulation, and its impact on the polycistronic mitochondrial transcript processing.

引用

页码：1622 / 1634

页数：13

共 40 条

[1] The Control Region of Mitochondrial DNA Shows an Unusual CpG and Non-CpG Methylation Pattern [J].