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Whole-genome bisulfite sequencing of multiple individuals reveals complementary roles of promoter and gene body methylation in transcriptional regulation

Lou, Shaoke ; Lee, Heung-Man ; Qin, Hao ; Li, Jing-Woei ; Gao, Zhibo ; Liu, Xin ; Chan, Landon L ; Kl Lam, Vincent ; So, Wing-Yee ; Wang, Ying ; Lok, Si ; Wang, Jun ; Ma, Ronald Cw ; Tsui, Stephen Kwok-Wing ; Chan, Juliana Cn ; Chan, Ting-Fung ; Yip, Kevin Y

Genome Biology (Online Edition), 2014-07, Vol.15 (7), p.408-408, Article 408 [Periódico revisado por pares]

England: BioMed Central Ltd

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Título:
Whole-genome bisulfite sequencing of multiple individuals reveals complementary roles of promoter and gene body methylation in transcriptional regulation
Autor: Lou, Shaoke ; Lee, Heung-Man ; Qin, Hao ; Li, Jing-Woei ; Gao, Zhibo ; Liu, Xin ; Chan, Landon L ; Kl Lam, Vincent ; So, Wing-Yee ; Wang, Ying ; Lok, Si ; Wang, Jun ; Ma, Ronald Cw ; Tsui, Stephen Kwok-Wing ; Chan, Juliana Cn ; Chan, Ting-Fung ; Yip, Kevin Y
Assuntos: Analysis ; Cell Line ; DNA Methylation ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Genetic aspects ; Genome, Human ; Humans ; Male ; Medical research ; Medicine, Experimental ; Models, Statistical ; Molecular Sequence Data ; Promoter Regions, Genetic ; RNA sequencing ; Sequence Analysis, DNA - methods ; Sequence Analysis, RNA ; Type 2 diabetes
É parte de: Genome Biology (Online Edition), 2014-07, Vol.15 (7), p.408-408, Article 408
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: DNA methylation is an important type of epigenetic modification involved in gene regulation. Although strong DNA methylation at promoters is widely recognized to be associated with transcriptional repression, many aspects of DNA methylation remain not fully understood, including the quantitative relationships between DNA methylation and expression levels, and the individual roles of promoter and gene body methylation. Here we present an integrated analysis of whole-genome bisulfite sequencing and RNA sequencing data from human samples and cell lines. We find that while promoter methylation inversely correlates with gene expression as generally observed, the repressive effect is clear only on genes with a very high DNA methylation level. By means of statistical modeling, we find that DNA methylation is indicative of the expression class of a gene in general, but gene body methylation is a better indicator than promoter methylation. These findings are general in that a model constructed from a sample or cell line could accurately fit the unseen data from another. We further find that promoter and gene body methylation have minimal redundancy, and either one is sufficient to signify low expression. Finally, we obtain increased modeling power by integrating histone modification data with the DNA methylation data, showing that neither type of information fully subsumes the other. Our results suggest that DNA methylation outside promoters also plays critical roles in gene regulation. Future studies on gene regulatory mechanisms and disease-associated differential methylation should pay more attention to DNA methylation at gene bodies and other non-promoter regions.
Editor: England: BioMed Central Ltd
Idioma: Inglês

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Whole-genome bisulfite sequencing of multiple individuals reveals complementary roles of promoter and gene body methylation in transcriptional regulation

Lou, Shaoke ; Lee, Heung-Man ; Qin, Hao ; Li, Jing-Woei ; Gao, Zhibo ; Liu, Xin ; Chan, Landon L ; Kl Lam, Vincent ; So, Wing-Yee ; Wang, Ying ; Lok, Si ; Wang, Jun ; Ma, Ronald Cw ; Tsui, Stephen Kwok-Wing ; Chan, Juliana Cn ; Chan, Ting-Fung ; Yip, Kevin Y

England: BioMed Central Ltd

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