Human body epigenome maps reveal noncanonical DNA methylation variation

Abstract

As part of the Epigenome Roadmap Project, genome-wide maps of DNA methylation and transcriptomes together with genomic DNA sequencing of 18 different primary human tissue types from 4 individuals are presented; analysis reveals widespread differential methylation of CG sites between tissues, and the presence of non-CG methylation in adult tissues. As part of the Epigenome Roadmap project, Joseph Ecker and colleagues provide genome-wide maps of DNA methylation and transcriptomes, in conjunction with genomic DNA sequencing, of 18 different primary human tissue types from four individuals. Analysis of the datasets reveals widespread differential methylation of CG sites between tissues, and methylation at regulatory elements generally has a negative correlation with gene expression as expected. A surprising amount of non-CG methylation is found in a subpopulation of cells in many tissues. Understanding the diversity of human tissues is fundamental to disease and requires linking genetic information, which is identical in most of an individual’s cells, with epigenetic mechanisms that could have tissue-specific roles. Surveys of DNA methylation in human tissues have established a complex landscape including both tissue-specific and invariant methylation patterns1,2. Here we report high coverage methylomes that catalogue cytosine methylation in all contexts for the major human organ systems, integrated with matched transcriptomes and genomic sequence. By combining these diverse data types with each individuals’ phased genome3, we identified widespread tissue-specific differential CG methylation (mCG), partially methylated domains, allele-specific methylation and transcription, and the unexpected presence of non-CG methylation (mCH) in almost all human tissues. mCH correlated with tissue-specific functions, and using this mark, we made novel predictions of genes that escape X-chromosome inactivation in specific tissues. Overall, DNA methylation in several genomic contexts varies substantially among human tissues.