title: Whole-genome bisulfite sequencing of multiple individuals reveals complementary roles of promoter and gene body methylation in transcriptional regulation.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Shaoke
authors: S
authors: Lou
authors: Heung-Man
authors: HM
authors: Lee
authors: Hao
authors: H
authors: Qin
authors: Jing-Woei
authors: JW
authors: Li
authors: Zhibo
authors: Z
authors: Gao
authors: Xin
authors: X
authors: Liu
authors: Landon L
authors: LL
authors: Chan
authors: Vincent
authors: V
authors: Kl Lam
authors: Wing-Yee
authors: WY
authors: So
authors: Ying
authors: Y
authors: Wang
authors: Si
authors: S
authors: Lok
authors: Jun
authors: J
authors: Wang
authors: Ronald Cw
authors: RC
authors: Ma
authors: Stephen Kwok-Wing
authors: SK
authors: Tsui
authors: Juliana Cn
authors: JC
authors: Chan
authors: Ting-Fung
authors: TF
authors: Chan
authors: Kevin Y
authors: KY
authors: Yip
mesh_terms: D002460:Cell Line; D019175:DNA Methylation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D008297:Male; D015233:Models, Statistical; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA / Q000379:methods*; D017423:Sequence Analysis, RNA