DNA methylation programming and reprogramming in primate embryonic stem cells

Netta Mendelson Cohen, Vikas Dighe, Gilad Landan, Sigrún Reynisdóttir, Arnar Palsson, Shoukhrat Mitalipov, Amos Tanay

    Research output: Contribution to journalArticle

    11 Citations (Scopus)

    Abstract

    DNA methylation is an important epigenetic mechanism, affecting normal development and playing a key role in reprogramming epigenomes during stem cell derivation. Here we report on DNA methylation patterns in native monkey embryonic stem cells (ESCs), fibroblasts, and ESCs generated through somatic cell nuclear transfer (SCNT), identifying and comparing epigenome programming and reprogramming. We characterize hundreds of regions that are hyper- or hypomethylated in fibroblasts compared to native ESCs and show that these are conserved in human cells and tissues. Remarkably, the vast majority of these regions are reprogrammed in SCNT ESCs, leading to almost perfect correlation between the epigenomic profiles of the native and reprogrammed lines. At least 58% of these changes are correlated in cis to transcription changes, Polycomb Repressive Complex-2 occupancy, or binding by the CTCF insulator. We also show that while epigenomic reprogramming is extensive and globally accurate, the efficiency of adding and stripping DNA methylation during reprogramming is regionally variable. In several cases, this variability results in regions that remain methylated in a fibroblast-like pattern even after reprogramming.

    Original languageEnglish (US)
    Pages (from-to)2193-2201
    Number of pages9
    JournalGenome Research
    Volume19
    Issue number12
    DOIs
    StatePublished - Dec 2009

    Fingerprint

    DNA Methylation
    Embryonic Stem Cells
    Primates
    Epigenomics
    Fibroblasts
    Polycomb Repressive Complex 2
    Haplorhini
    Stem Cells

    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)

    Cite this

    Cohen, N. M., Dighe, V., Landan, G., Reynisdóttir, S., Palsson, A., Mitalipov, S., & Tanay, A. (2009). DNA methylation programming and reprogramming in primate embryonic stem cells. Genome Research, 19(12), 2193-2201. https://doi.org/10.1101/gr.096685.109

    DNA methylation programming and reprogramming in primate embryonic stem cells. / Cohen, Netta Mendelson; Dighe, Vikas; Landan, Gilad; Reynisdóttir, Sigrún; Palsson, Arnar; Mitalipov, Shoukhrat; Tanay, Amos.

    In: Genome Research, Vol. 19, No. 12, 12.2009, p. 2193-2201.

    Research output: Contribution to journalArticle

    Cohen, NM, Dighe, V, Landan, G, Reynisdóttir, S, Palsson, A, Mitalipov, S & Tanay, A 2009, 'DNA methylation programming and reprogramming in primate embryonic stem cells', Genome Research, vol. 19, no. 12, pp. 2193-2201. https://doi.org/10.1101/gr.096685.109
    Cohen, Netta Mendelson ; Dighe, Vikas ; Landan, Gilad ; Reynisdóttir, Sigrún ; Palsson, Arnar ; Mitalipov, Shoukhrat ; Tanay, Amos. / DNA methylation programming and reprogramming in primate embryonic stem cells. In: Genome Research. 2009 ; Vol. 19, No. 12. pp. 2193-2201.
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