title: A diverse epigenetic landscape at human exons with implication for expression.
abstract: 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 hypomethylated 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.
authors.affiliation: Department of Computer Science, University of California at Berkeley, Berkeley, CA 94720 USA.
authors.forename: Meromit
authors.initials: M
authors.lastname: Singer
authors.affiliation: Department of Molecular & Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: Idit
authors.initials: I
authors.lastname: Kosti
authors.affiliation: Department of Computer Science, University of California at Berkeley, Berkeley, CA 94720 USA Department of Mathematics, University of California at Berkeley, Berkeley, CA 94720, USA Department of Molecular & Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA.
authors.forename: Lior
authors.initials: L
authors.lastname: Pachter
authors.affiliation: Department of Molecular & Cell Biology, University of California at Berkeley, Berkeley, CA 94720, USA yaelmg@tx.technion.ac.il.
authors.forename: Yael
authors.initials: Y
authors.lastname: Mandel-Gutfreund
mesh_terms: D004247:DNA / Q000737:chemistry / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005091:Exons; D006801:Humans; D007438:Introns
chemical_list: D004247:DNA