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N6-methyldeoxyadenosine directs nucleosome positioning in Tetrahymena DNA

Background N6-methyldeoxyadenosine (6mA or m6dA) was shown more than 40 years ago in simple eukaryotes. Recent studies revealed the presence of 6mA in more prevalent eukaryotes, even in vertebrates. However, functional characterizations have been limited. Results We use Tetrahymena thermophila as a...

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Published in:Genome Biology 2018-11, Vol.19 (1), p.200-200, Article 200
Main Authors: Luo, Guan-Zheng, Hao, Ziyang, Luo, Liangzhi, Shen, Mingren, Sparvoli, Daniela, Zheng, Yuqing, Zhang, Zijie, Weng, Xiaocheng, Chen, Kai, Cui, Qiang, Turkewitz, Aaron P., He, Chuan
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cited_by cdi_FETCH-LOGICAL-c3843-88e9289d953a3b8174822f5cd9bf2a40a47473851195fbde71ab170723e98f5d3
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container_issue 1
container_start_page 200
container_title Genome Biology
container_volume 19
creator Luo, Guan-Zheng
Hao, Ziyang
Luo, Liangzhi
Shen, Mingren
Sparvoli, Daniela
Zheng, Yuqing
Zhang, Zijie
Weng, Xiaocheng
Chen, Kai
Cui, Qiang
Turkewitz, Aaron P.
He, Chuan
description Background N6-methyldeoxyadenosine (6mA or m6dA) was shown more than 40 years ago in simple eukaryotes. Recent studies revealed the presence of 6mA in more prevalent eukaryotes, even in vertebrates. However, functional characterizations have been limited. Results We 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. Conclusions These findings uncover a mechanism by which DNA 6mA assists to shape the nucleosome positioning and potentially affects gene expression.
doi_str_mv 10.1186/s13059-018-1573-3
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Recent studies revealed the presence of 6mA in more prevalent eukaryotes, even in vertebrates. However, functional characterizations have been limited. Results We 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. 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Recent studies revealed the presence of 6mA in more prevalent eukaryotes, even in vertebrates. However, functional characterizations have been limited. Results We 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. 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1474-760X
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source Publicly Available Content Database (Proquest) (PQ_SDU_P3); PubMed Central
subjects Computer applications
Deoxyribonucleic acid
DNA
DNA methylation
Enzymes
Epigenetics
Eukaryotes
Gene expression
Genomes
Integrated software
Methyltransferase
N6-methyladenosine
Nucleosomes
Organisms
Prokaryotes
Tetrahymena
Transcription
title N6-methyldeoxyadenosine directs nucleosome positioning in Tetrahymena DNA
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