Publication Date:
2009-10-16
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857523/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857523/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉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 -- R01 HG003523/HG/NHGRI NIH HHS/ -- R01 HG003523-01/HG/NHGRI NIH HHS/ -- R01 HG003523-02/HG/NHGRI NIH HHS/ -- R01 HG003523-03/HG/NHGRI NIH HHS/ -- U01 1U01ES017166-01/ES/NIEHS NIH HHS/ -- U01 ES017166/ES/NIEHS NIH HHS/ -- England -- Nature. 2009 Nov 19;462(7271):315-22. doi: 10.1038/nature08514. Epub 2009 Oct 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19829295" target="_blank"〉PubMed〈/a〉
Keywords:
Cell Line
;
Cluster Analysis
;
DNA/metabolism
;
*DNA Methylation
;
DNA-Binding Proteins/metabolism
;
Embryonic Stem Cells/metabolism
;
*Epigenesis, Genetic
;
Genome/*genetics
;
Humans
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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