Human Body Epigenome Maps Reveal Noncanonical DNA Methylation Variation

By Matthew D. Schultz, Yupeng He, J. Whitaker, M. Hariharan, Eran A. Mukamel, Danny Leung, N. Rajagopal, Joseph R. Nery, M. Urich, Huaming Chen and 9 more. Nature, 2015

641 citations recorded by the source corpus.

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 patterns. 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 genome, 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.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5b8542baa9f0992d89a146119656a09750bb2ebf

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Genetics

In Molecular Biology

Citations in the corpus

Mapping genome-wide transcription-factor binding sites using DAP-seq (2017, background): “Cell-line and tissue-specific DNA modifications are central features of multicellular development, and there are substantial differences in DNA methylation between different cell and tissue types in both humans and plants 19,20 .”
Editing DNA methylation in the mammalian genome (2016, neutral): “DMRs upstream of mouse MyoD gene were defined based on human/mouse genome homology (Schultz et al., 2015).”
DNA methylation aging clocks: challenges and recommendations (2019, background): “3) in normal conditions is estimated at 15–21% [137, 138] (see Fig.”
Landscape of X chromosome inactivation across human tissues (2016, neutral): “However, the extent to which XCI is shared between cells and tissues remains poorly characterized 3,4 , as does the degree to which incomplete XCI manifests as detectable sex differences in gene expression 5 and phenotypic traits 6 .”
Epigenomic diversity in a global collection of Arabidopsis thaliana accessions (2016, positive): “, 2015) or adult tissues (Schultz et al., 2015) are associated with developmental control genes.”