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  • 1
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    Human DNA methylomes at base resolution show widespread epigenomic differences (2009)
    Nature Publishing Group (NPG)
    Details
    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
    Published by Nature Publishing Group (NPG)
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  • 2
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    Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells (2011)
    Nature Publishing Group (NPG)
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    Publication Date: 2011-02-04
    Description: Induced pluripotent stem cells (iPSCs) offer immense potential for regenerative medicine and studies of disease and development. Somatic cell reprogramming involves epigenomic reconfiguration, conferring iPSCs with characteristics similar to embryonic stem (ES) cells. However, it remains unknown how complete the reestablishment of ES-cell-like DNA methylation patterns is throughout the genome. Here we report the first whole-genome profiles of DNA methylation at single-base resolution in five human iPSC lines, along with methylomes of ES cells, somatic cells, and differentiated iPSCs and ES cells. iPSCs show significant reprogramming variability, including somatic memory and aberrant reprogramming of DNA methylation. iPSCs share megabase-scale differentially methylated regions proximal to centromeres and telomeres that display incomplete reprogramming of non-CG methylation, and differences in CG methylation and histone modifications. Lastly, differentiation of iPSCs into trophoblast cells revealed that errors in reprogramming CG methylation are transmitted at a high frequency, providing an iPSC reprogramming signature that is maintained after differentiation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100360/" 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/PMC3100360/" 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 -- Kida, Yasuyuki S -- Hawkins, R David -- Nery, Joseph R -- Hon, Gary -- Antosiewicz-Bourget, Jessica -- O'Malley, Ronan -- Castanon, Rosa -- Klugman, Sarit -- Downes, Michael -- Yu, Ruth -- Stewart, Ron -- Ren, Bing -- Thomson, James A -- Evans, Ronald M -- Ecker, Joseph R -- 1U01ES017166-01/ES/NIEHS NIH HHS/ -- DK062434/DK/NIDDK NIH HHS/ -- P30 CA014195/CA/NCI NIH HHS/ -- U01 ES017166/ES/NIEHS NIH HHS/ -- U01 ES017166-01/ES/NIEHS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Mar 3;471(7336):68-73. doi: 10.1038/nature09798. Epub 2011 Feb 2.〈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/21289626" target="_blank"〉PubMed〈/a〉
    Keywords: Cell Differentiation/genetics ; Cell Line ; Cellular Reprogramming/*genetics ; CpG Islands/genetics ; DNA Methylation/*genetics ; Embryonic Stem Cells/cytology/metabolism ; Epigenomics ; Epistasis, Genetic/*genetics ; Fibroblasts/cytology/metabolism ; Genome, Human/*genetics ; Histones/metabolism ; Humans ; Induced Pluripotent Stem Cells/cytology/*metabolism ; Trophoblasts/cytology/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Published by Nature Publishing Group (NPG)
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  • 3
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    Predictive chromatin signatures in the mammalian genome (2009)
    Oxford University Press
    Details
    Publication Date: 2009-10-06
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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