Dynamic DNA methylation across diverse human cell lines and tissues

By K. Varley, Jason Gertz, K. Bowling, S. Parker, Timothy E. Reddy, Florencia Pauli-Behn, M. Cross, B. Williams, John A. Stamatoyannopoulos, Gregory E. Crawford and 3 more. Genome Research, 2013

705 citations recorded by the source corpus.

As studies of DNA methylation increase in scope, it has become evident that methylation has a complex relationship with gene expression, plays an important role in defining cell types, and is disrupted in many diseases. We describe large-scale single-base resolution DNA methylation profiling on a diverse collection of 82 human cell lines and tissues using reduced representation bisulfite sequencing (RRBS). Analysis integrating RNA-seq and ChIP-seq data illuminates the functional role of this dynamic mark. Loci that are hypermethylated across cancer types are enriched for sites bound by NANOG in embryonic stem cells, which supports and expands the model of a stem/progenitor cell signature in cancer. CpGs that are hypomethylated across cancer types are concentrated in megabase-scale domains that occur near the telomeres and centromeres of chromosomes, are depleted of genes, and are enriched for cancer-specific EZH2 binding and H3K27me3 (repressive chromatin). In noncancer samples, there are cell-type specific methylation signatures preserved in primary cell lines and tissues as well as methylation differences induced by cell culture. The relationship between methylation and expression is context-dependent, and we find that CpG-rich enhancers bound by EP300 in the bodies of expressed genes are unmethylated despite the dense gene-body methylation surrounding them. Non-CpG cytosine methylation occurs in human somatic tissue, is particularly prevalent in brain tissue, and is reproducible across many individuals. This study provides an atlas of DNA methylation across diverse and well-characterized samples and enables new discoveries about DNA methylation and its role in gene regulation and disease.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/27b4f3c956493f7536f602922369a1654dc19a61

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Citations in the corpus

Global Epigenomic Reconfiguration During Mammalian Brain Development (2013, background): “mCHhas previously been identified throughout the genome of the adult mouse brain (20) and at several hundred genomic positions in the human adult brain (21).”
Joint profiling of chromatin accessibility, DNA methylation and transcription in single cells (2017, methodology): “From the RNA-seq data we discarded cells that had (1) less than 300,000 reads mapped (2) more than 15% of total reads mapped to mitochondrial genes, (3) less than 2,000 genes expressed.”
Gene Body Methylation can alter Gene Expression and is a Therapeutic Target in Cancer (2014, background): “Recently, more detailed genome-wide studies have also demonstrated that DNA methylation in transcribed regions is correlated with gene expression (Kulis et al., 2012; Maunakea et al., 2010; Varley et al., 2013).”
High-resolution genome-wide DNA methylation maps of mouse primary female dermal fibroblasts and keratinocytes (2014, neutral): “…cytosine methylation have been published for mammals reinforcing the idea that CG demethylation occurs in clusters, typically in regions of high CG density [5,18-20 , Here, we compared the DNA methylation maps in newborn female mouse primary dermal fibroblasts and keratinocytes derived from skin.”
Human Body Epigenome Maps Reveal Noncanonical DNA Methylation Variation (2015, neutral): “9 (837) 10 (1,133) 11 (867) 12 (845) 13 (1,158) 14 (325) 15,16 (49, 660) 17,18 (35, 828) 19 (1,135) 20 (434)”