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First published online March 7, 2008

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Dnmt1: a direct transcription repressor?

The regulation of gene expression during development often involves epigenetic changes. In vertebrates, for example, the cytosine methyltransferase Dnmt1 is essential for gene silencing in early embryos. It is widely thought that Dnmt1 fulfils this role by maintaining DNA methylation at inactive genes. However, on p. 1295, Richard Meehan and colleagues challenge this dogma by showing that xDnmt1 regulates gene silencing in early Xenopus embryos independently of its DNA methyltransferase activity. The researchers show that a partial reduction of xDnmt1 protein levels by morpholinos prematurely activates zygotic gene expression before the pre-midblastula transition, when these genes are normally activated in Xenopus embryos. However, this premature gene activation occurs without any decrease in DNA methylation, either globally or at specific loci. Furthermore, the injection of an mRNA encoding a catalytically inactive form of human DNMT1 rescues the morpholino-treated embryos. These and other data suggest that xDnmt1 (and possibly mammalian Dnmt1) regulates embryonic gene silencing both through its catalytic activity and by acting as a direct, non-catalytic transcription repressor protein.

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Related articles in Development:

xDnmt1 regulates transcriptional silencing in pre-MBT Xenopus embryos independently of its catalytic function

Donncha S. Dunican, Alexey Ruzov, Jamie A. Hackett, and Richard R. Meehan
Development 2008 135: 1295-1302. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?