N6-methyldeoxyadenosine directs nucleosome positioning in Tetrahymena DNA

被引：49

作者：

Luo, Guan-Zheng ^{[1
,2
,3
,4
]}

Hao, Ziyang ^{[2
,3
,4
]}

Luo, Liangzhi ^{[2
,3
,4
,5
]}

Shen, Mingren ^{[6
,7
]}

Sparvoli, Daniela ^{[8
]}

Zheng, Yuqing ^{[6
,7
]}

Zhang, Zijie ^{[2
,3
,4
]}

Weng, Xiaocheng ^{[2
,3
,4
]}

Chen, Kai ^{[2
,3
,4
]}

Cui, Qiang ^{[6
,7
]}

Turkewitz, Aaron P. ^{[8
]}

He, Chuan ^{[2
,3
,4
]}

机构：

[1] Sun Yat Sen Univ, Sch Life Sci, State Key Lab Biocontrol, MOE Key Lab Gene Funct & Regulat, Guangzhou 510060, Guangdong, Peoples R China

[2] Univ Chicago, Dept Biochem & Mol Biol, Dept Chem, 929 East 57th St, Chicago, IL 60637 USA

[3] Univ Chicago, Inst Biophys Dynam, 929 East 57th St, Chicago, IL 60637 USA

[4] Univ Chicago, Howard Hughes Med Inst, 929 East 57th St, Chicago, IL 60637 USA

[5] Guizhou Univ, Key Lab Green Pesticide & Agr Bioengn, Minist Educ, Guiyang 550025, Guizhou, Peoples R China

[6] Univ Wisconsin, Dept Chem, Grad Program Biophys, 1101 Univ Ave, Madison, WI 53706 USA

[7] Univ Wisconsin, Inst Theoret Chem, 1101 Univ Ave, Madison, WI 53706 USA

[8] Univ Chicago, Dept Mol Genet & Cell Biol, 920 East 58th St, Chicago, IL 60637 USA

来源：

GENOME BIOLOGY | 2018年 / 19卷

基金：

美国国家卫生研究院; 中国国家自然科学基金; 美国国家科学基金会;

关键词：

N-6-methyldeoxyadenosine; 6mA; m(6)dA; DNA methylation; Nucleosome; Methyltransferase; FORCE-FIELD; METHYLATION; ADENINE; N-6-ADENINE; EUKARYOTE; SEQUENCE; PARTICLE; AMBER; VISUALIZATION; THERMOPHILA;

D O I：

10.1186/s13059-018-1573-3

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

BackgroundN(6)-methyldeoxyadenosine (6mA or m(6)dA) was shown more than 40years ago in simple eukaryotes. Recent studies revealed the presence of 6mA in more prevalent eukaryotes, even in vertebrates. However, functional characterizations have been limited.ResultsWe use Tetrahymena thermophila as a model organism to examine the effects of 6mA on nucleosome positioning. Independent methods reveal the enrichment of 6mA near and after transcription start sites with a periodic pattern and anti-correlation relationship with the positions of nucleosomes. The distribution pattern can be recapitulated by in vitro nucleosome assembly on native Tetrahymena genomic DNA but not on DNA without 6mA. Model DNA containing artificially installed 6mA resists nucleosome assembling compared to unmodified DNA in vitro. Computational simulation indicates that 6mA increases dsDNA rigidity, which disfavors nucleosome wrapping. Knockout of a potential 6mA methyltransferase leads to a transcriptome-wide change of gene expression.ConclusionsThese findings uncover a mechanism by which DNA 6mA assists to shape the nucleosome positioning and potentially affects gene expression.

引用

页数：12

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