Human DNA methylomes at base resolution show widespread epigenomic differences

Ryan Lister, Mattia Pelizzola, Robert H. Dowen, R. David Hawkins, Gary Hon, Julian Tonti-Filippini, Joseph R. Nery, Leonard Lee, Zhen Ye, Que Minh Ngo, Lee Edsall, Jessica Antosiewicz-Bourget, Ron Stewart, Victor Ruotti, A. Harvey Millar, James A. Thomson, Bing Ren, Joseph R. Ecker

Research output: Contribution to journalArticle

2613 Citations (Scopus)

Abstract

DNA cytosine methylation is a central epigenetic modification that has essential roles in cellular processes including genome regulation, development and disease. Here we present the first genome-wide, single-base-resolution maps of methylated cytosines in a mammalian genome, from both human embryonic stem cells and fetal fibroblasts, along with comparative analysis of messenger RNA and small RNA components of the transcriptome, several histone modifications, and sites of DNAĝ€"protein interaction for several key regulatory factors. Widespread differences were identified in the composition and patterning of cytosine methylation between the two genomes. Nearly one-quarter of all methylation identified in embryonic stem cells was in a non-CG context, suggesting that embryonic stem cells may use different methylation mechanisms to affect gene regulation. Methylation in non-CG contexts showed enrichment in gene bodies and depletion in protein binding sites and enhancers. Non-CG methylation disappeared upon induced differentiation of the embryonic stem cells, and was restored in induced pluripotent stem cells. We identified hundreds of differentially methylated regions proximal to genes involved in pluripotency and differentiation, and widespread reduced methylation levels in fibroblasts associated with lower transcriptional activity. These reference epigenomes provide a foundation for future studies exploring this key epigenetic modification in human disease and development.

Original languageEnglish (US)
Pages (from-to)315-322
Number of pages8
JournalNature
Volume462
Issue number7271
DOIs
StatePublished - Nov 19 2009

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Epigenomics
Methylation
Cytosine
DNA
Embryonic Stem Cells
Genome
Histone Code
Fibroblasts
Genes
Induced Pluripotent Stem Cells
Human Development
DNA Methylation
Transcriptome
Protein Binding
Binding Sites
RNA
Messenger RNA
Proteins

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Lister, R., Pelizzola, M., Dowen, R. H., Hawkins, R. D., Hon, G., Tonti-Filippini, J., ... Ecker, J. R. (2009). Human DNA methylomes at base resolution show widespread epigenomic differences. Nature, 462(7271), 315-322. https://doi.org/10.1038/nature08514

Human DNA methylomes at base resolution show widespread epigenomic differences. / Lister, Ryan; Pelizzola, Mattia; Dowen, Robert H.; Hawkins, R. David; Hon, Gary; Tonti-Filippini, Julian; Nery, Joseph R.; Lee, Leonard; Ye, Zhen; Ngo, Que Minh; Edsall, Lee; Antosiewicz-Bourget, Jessica; Stewart, Ron; Ruotti, Victor; Millar, A. Harvey; Thomson, James A.; Ren, Bing; Ecker, Joseph R.

In: Nature, Vol. 462, No. 7271, 19.11.2009, p. 315-322.

Research output: Contribution to journalArticle

Lister, R, Pelizzola, M, Dowen, RH, Hawkins, RD, Hon, G, Tonti-Filippini, J, Nery, JR, Lee, L, Ye, Z, Ngo, QM, Edsall, L, Antosiewicz-Bourget, J, Stewart, R, Ruotti, V, Millar, AH, Thomson, JA, Ren, B & Ecker, JR 2009, 'Human DNA methylomes at base resolution show widespread epigenomic differences', Nature, vol. 462, no. 7271, pp. 315-322. https://doi.org/10.1038/nature08514
Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J et al. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature. 2009 Nov 19;462(7271):315-322. https://doi.org/10.1038/nature08514
Lister, Ryan ; Pelizzola, Mattia ; Dowen, Robert H. ; Hawkins, R. David ; Hon, Gary ; Tonti-Filippini, Julian ; Nery, Joseph R. ; Lee, Leonard ; Ye, Zhen ; Ngo, Que Minh ; Edsall, Lee ; Antosiewicz-Bourget, Jessica ; Stewart, Ron ; Ruotti, Victor ; Millar, A. Harvey ; Thomson, James A. ; Ren, Bing ; Ecker, Joseph R. / Human DNA methylomes at base resolution show widespread epigenomic differences. In: Nature. 2009 ; Vol. 462, No. 7271. pp. 315-322.
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