Gene Set: WAGSCHAL_EHMT2_TARGETS_UP

Standard name WAGSCHAL_EHMT2_TARGETS_UP
Systematic name M2189
Brief description Genes up-regulated in placenta of mice with EHMT2 [GeneID=10919] knocked out.
Full description or 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, 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.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 18039842   Authors: Wagschal A,Sutherland HG,Woodfine K,Henckel A,Chebli K,Schulz R,Oakey RJ,Bickmore WA,Feil R
Exact source Table 1AS: SLR > 0
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Organism Mus musculus
Contributed by Arthur Liberzon (Broad Institute)
Source platform MOE430A
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.1: First introduced

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