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  • G9a Histone Methyltransferase Contributes to Imprinting in the Mouse Placenta

    Author(s)
    Wagschal, Alexandre
    Sutherland, Heidi
    Woodfine, Kathryn
    Henckel, Amandine
    Chebli, Karim
    Schulz, Reiner
    Oakey, Rebecca
    Bickmore, Wendy
    Feil, Robert
    Griffith University Author(s)
    Sutherland, Heidi
    Year published
    2008
    Metadata
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    Abstract
    Whereas DNA methylation is essential for genomic imprinting, the importance of histone methylation in the allelic expression of imprinted genes is unclear. Imprinting control regions (ICRs), however, are marked by histone H3-K9 methylation on their DNA-methylated allele. In the placenta, the paternal silencing along the Kcnq1 domain on distal chromosome 7 also correlates with the presence of H3-K9 methylation, but imprinted repression at these genes is maintained independently of DNA methylation. To explore which histone methyltransferase (HMT) could mediate the allelic H3-K9 methylation on distal chromosome 7, and at ICRs, ...
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    Whereas DNA methylation is essential for genomic imprinting, the importance of histone methylation in the allelic expression of imprinted genes is unclear. Imprinting control regions (ICRs), however, are marked by histone H3-K9 methylation on their DNA-methylated allele. In the placenta, the paternal silencing along the Kcnq1 domain on distal chromosome 7 also correlates with the presence of H3-K9 methylation, but imprinted repression at these genes is maintained independently of DNA methylation. To explore which histone methyltransferase (HMT) could mediate the allelic H3-K9 methylation on distal chromosome 7, and at ICRs, we generated mouse conceptuses deficient for the SET domain protein G9a. We found that in the embryo and placenta, the differential DNA methylation at ICRs and imprinted genes is maintained in the absence of G9a. Accordingly, in embryos, imprinted gene expression was unchanged at the domains analyzed, in spite of a global loss of H3-K9 dimethylation (H3K9me2). In contrast, the placenta-specific imprinting of genes on distal chromosome 7 is impaired in the absence of G9a, and this correlates with reduced levels of H3K9me2 and H3K9me3. These findings provide the first evidence for the involvement of an HMT and suggest that histone methylation contributes to imprinted gene repression in the trophoblast.
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    Journal Title
    Molecular and Cellular Biology
    Volume
    28
    Issue
    3
    DOI
    https://doi.org/10.1128/MCB.01111-07
    Subject
    Developmental Genetics (incl. Sex Determination)
    Biological Sciences
    Medical and Health Sciences
    Publication URI
    http://hdl.handle.net/10072/40306
    Collection
    • Journal articles

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