A diverse epigenetic landscape at human exons with implication for expression

被引:49
作者
Singer, Meromit [1 ]
Kosti, Idit [2 ]
Pachter, Lior [1 ,3 ,4 ]
Mandel-Gutfreund, Yael [2 ]
机构
[1] Univ Calif Berkeley, Dept Comp Sci, Berkeley, CA 94720 USA
[2] Technion Israel Inst Technol, Fac Biol, IL-32000 Haifa, Israel
[3] Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA
[4] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
关键词
BODY-SPECIFIC METHYLATION; DNA-METHYLATION; GENE-EXPRESSION; PROMOTER; REVEALS; TRANSCRIPTION; ROLES; SITES;
D O I
10.1093/nar/gkv153
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
DNA methylation is an important epigenetic marker associated with gene expression regulation in eukaryotes. While promoter methylation is relatively well characterized, the role of intragenic DNA methylation remains unclear. Here, we investigated the relationship of DNA methylation at exons and flanking introns with gene expression and histone modifications generated from a human fibroblast cell-line and primary B cells. Consistent with previous work we found that intragenic methylation is positively correlated with gene expression and that exons are more highly methylated than their neighboring intronic environment. Intriguingly, in this study we identified a unique subset of hypo-methylated exons that demonstrate significantly lower methylation levels than their surrounding introns. Furthermore, we observed a negative correlation between exon methylation and the density of the majority of histone modifications. Specifically, we demonstrate that hypo-methylated exons at highly expressed genes are associated with open chromatin and have a characteristic histone code comprised of significantly high levels of histone markings. Overall, our comprehensive analysis of the human exome supports the presence of regulatory hypomethylated exons in protein coding genes. In particular our results reveal a previously unrecognized diverse and complex role of the epigenetic landscape within the gene body.
引用
收藏
页码:3498 / 3508
页数:11
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