Methylation status of imprinting centers for H19/IGF2 and SNURF/SNRPN in primate embryonic stem cells

Shoukhrat Mitalipov, Lisa Clepper, Hathaitip Sritanaudomchai, Akihisa Fujimoto, Don Wolf

    Research output: Contribution to journalArticle

    38 Citations (Scopus)

    Abstract

    Embryonic stem cells (ESCs) hold promise for cell and tissue replacement approaches to treating human diseases based on their capacity to differentiate into a wide variety of somatic cells and tissues. However, long-term in vitro culture and manipulations of ESCs may adversely affect their epigenetic integrity, including imprinting. We have recently reported aberrant biallelic expression of IGF2 and H19 in several rhesus monkey ESC lines, whereas SNRPN and NDN were normally imprinted and expressed predominantly from the paternal allele. The dysregulation of IGF2 and H19 that is associated with tumorigenesis in humans may result from improper maintenance of allele-specific methylation patterns at an imprinting center (IC) upstream of H19. To test this possibility, we performed methylation analysis of several monkey ESC lines by genomic bisulfite sequencing. We investigated methylation profiles of CpG islands within the IGF2/H19 IC harboring the CTCF-6 binding site. In addition, the methylation status of the IC within the promoter/ exon 1 of SNURF/SNRPN known as the Prader-Willi syndrome IC was examined. Our results demonstrate abnormal hypermethylation within the IGF2/H19 IC in all analyzed ESC lines, whereas the SNURF/SNRPN IC was differentially methylated, consistent with monoallelic expression.

    Original languageEnglish (US)
    Pages (from-to)581-588
    Number of pages8
    JournalStem Cells
    Volume25
    Issue number3
    DOIs
    StatePublished - Mar 2007

    Fingerprint

    snRNP Core Proteins
    Embryonic Stem Cells
    Methylation
    Primates
    Cell Line
    Alleles
    Prader-Willi Syndrome
    CpG Islands
    Macaca mulatta
    Epigenomics
    Haplorhini
    Exons
    Carcinogenesis
    Binding Sites
    Maintenance

    Keywords

    • Embryonic stem cells
    • Imprinting
    • Methylation
    • Monkey

    ASJC Scopus subject areas

    • Cell Biology

    Cite this

    Methylation status of imprinting centers for H19/IGF2 and SNURF/SNRPN in primate embryonic stem cells. / Mitalipov, Shoukhrat; Clepper, Lisa; Sritanaudomchai, Hathaitip; Fujimoto, Akihisa; Wolf, Don.

    In: Stem Cells, Vol. 25, No. 3, 03.2007, p. 581-588.

    Research output: Contribution to journalArticle

    Mitalipov, Shoukhrat ; Clepper, Lisa ; Sritanaudomchai, Hathaitip ; Fujimoto, Akihisa ; Wolf, Don. / Methylation status of imprinting centers for H19/IGF2 and SNURF/SNRPN in primate embryonic stem cells. In: Stem Cells. 2007 ; Vol. 25, No. 3. pp. 581-588.
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