G9a histone methyltransferase contributes to imprinting in the mouse placenta
Wagschal, Alexandre, Sutherland, Heidi G., Woodfine, Kathryn, Henckel, Amandine, Chebli, Karim, Schulz, Reiner, Oakey, Rebecca J., Bickmore, Wendy A., & Feil, Robert (2008) G9a histone methyltransferase contributes to imprinting in the mouse placenta. Molecular and Cellular Biology, 28(3), pp. 1104-1113.
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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|Item Type:||Journal Article|
|Additional Information:||Articles free to read on journal website after 6 months|
|Keywords:||histone methyltransferase; histone methyltransferase G9a; unclassified drug; allele; animal tissue; article; chromosome 7; controlled study; DNA methylation; enzyme activity; gene expression; gene repression; gene silencing; genome imprinting; mouse; nonh|
|Subjects:||Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > CLINICAL SCIENCES (110300) > Medical Genetics (excl. Cancer Genetics) (110311)|
|Divisions:||Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Deposited On:||23 Sep 2014 22:33|
|Last Modified:||05 Feb 2015 05:57|
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