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XB-ART-11499
Genes Dev February 1, 2000; 14 (3): 313-27.

Transient depletion of xDnmt1 leads to premature gene activation in Xenopus embryos.



Abstract
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.

PubMed ID: 10673503
PMC ID: PMC316362
Article link: Genes Dev

Genes referenced: cer1 dnmt1 gal.2 h4c4 hdac3 hoxb3 hoxb9 odc1 otx2 pcna tbx2 tbxt
Antibodies: Dnmt1 Ab2 Methyl Cytosine Ab2


Article Images: [+] show captions
References:
Almouzni, 1995, Pubmed, Xenbase [+]


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