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Vol. 14, No. 3, pp. 313-327, February 1, 2000
Genes and Development Group, Department of Biomedical Sciences,
University of Edinburgh, Edinburgh EH8 9XD Scotland, UK
In Xenopus laevis zygotic transcription begins at the
midblastula transition (MBT). Prior to this the genome is organized into chromatin that facilitates rapid cycles of DNA replication but not
transcription. Here we demonstrate that DNA methylation contributes to
the overall transcriptional silencing before MBT. Transient depletion
of the maternal DNA methyltransferase (xDnmt1) by anti sense
RNA during cleavage stages is associated with a decrease in the genomic
5-methyl-cytosine content and leads to the activation of zygotic
transcription approximately two cell cycles earlier than normal.
Hypomethylation allows the early expression of mesodermal marker genes
such as Xbra, Cerberus, and Otx2, which are
subsequently down-regulated during gastrulation of the
xDnmt1-depleted embryos. The temporal switch in gene expression
may account for the appearance of body plan defects that we observe.
Loss of xDnmt1 can be rescued by the coinjection of mouse or
human Dnmt1 protein. These results demonstrate that DNA methylation has
a role in the regulation of immediately early genes in Xenopus
at MBT.
[Key Words: 5-methylcytosine; Xenopus; DNA methyltransferase; antisense RNA; MBT]
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