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DNMT1: a direct transcriptional repressor?
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In vertebrates, 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. Richard Meehan and colleagues challenge this dogma by showing in early Xenopus laevis embryos that xDnmt1 regulates gene silencing independently of its DNA methyltransferase activity.
The researchers show that a partial reduction of xDnmt1 protein levels by morpholino injection prematurely activates zygotic gene expression in Xenopus embryos. However, this premature gene activation occurs without any decrease in DNA methylation, either globally or at specific loci. The injection of an mRNA encoding a catalytically inactive form of human DNMT1 rescues transcription repression in morpholino-treated embryos. These and other data suggest that xDnmt1 (and possibly mammalian Dnmt1) regulates embryonic gene silencing both through its catalytic methyltransferase activity and by acting as a direct, non-catalytic transcription repressor protein. The paper appears in the latest edition of Development
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