Human DNA methylomes at base resolution show widespread epigenomic differences View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-11

AUTHORS

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

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 DNA-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. More... »

PAGES

315

References to SciGraph publications

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  • Journal

    TITLE

    Nature

    ISSUE

    7271

    VOLUME

    462

    Related Patents

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature08514

    DOI

    http://dx.doi.org/10.1038/nature08514

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1001394004

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/19829295


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