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Dynamic DNA methylation across diverse human cell lines and tissues.

Publication ,  Journal Article
Varley, KE; Gertz, J; Bowling, KM; Parker, SL; Reddy, TE; Pauli-Behn, F; Cross, MK; Williams, BA; Stamatoyannopoulos, JA; Crawford, GE ...
Published in: Genome Res
March 2013

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.

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Published In

Genome Res

DOI

EISSN

1549-5469

Publication Date

March 2013

Volume

23

Issue

3

Start / End Page

555 / 567

Location

United States

Related Subject Headings

  • Sulfites
  • Sequence Analysis, DNA
  • Sequence Alignment
  • Promoter Regions, Genetic
  • Oligonucleotide Array Sequence Analysis
  • Humans
  • Gene Expression Regulation
  • Gene Expression Profiling
  • DNA Methylation
  • CpG Islands
 

Citation

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Varley, K. E., Gertz, J., Bowling, K. M., Parker, S. L., Reddy, T. E., Pauli-Behn, F., … Myers, R. M. (2013). Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res, 23(3), 555–567. https://doi.org/10.1101/gr.147942.112
Varley, Katherine E., Jason Gertz, Kevin M. Bowling, Stephanie L. Parker, Timothy E. Reddy, Florencia Pauli-Behn, Marie K. Cross, et al. “Dynamic DNA methylation across diverse human cell lines and tissues.Genome Res 23, no. 3 (March 2013): 555–67. https://doi.org/10.1101/gr.147942.112.
Varley KE, Gertz J, Bowling KM, Parker SL, Reddy TE, Pauli-Behn F, et al. Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res. 2013 Mar;23(3):555–67.
Varley, Katherine E., et al. “Dynamic DNA methylation across diverse human cell lines and tissues.Genome Res, vol. 23, no. 3, Mar. 2013, pp. 555–67. Pubmed, doi:10.1101/gr.147942.112.
Varley KE, Gertz J, Bowling KM, Parker SL, Reddy TE, Pauli-Behn F, Cross MK, Williams BA, Stamatoyannopoulos JA, Crawford GE, Absher DM, Wold BJ, Myers RM. Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res. 2013 Mar;23(3):555–567.

Published In

Genome Res

DOI

EISSN

1549-5469

Publication Date

March 2013

Volume

23

Issue

3

Start / End Page

555 / 567

Location

United States

Related Subject Headings

  • Sulfites
  • Sequence Analysis, DNA
  • Sequence Alignment
  • Promoter Regions, Genetic
  • Oligonucleotide Array Sequence Analysis
  • Humans
  • Gene Expression Regulation
  • Gene Expression Profiling
  • DNA Methylation
  • CpG Islands