Surviving Methyl Deficiency

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Science  24 Sep 2010:
Vol. 329, Issue 5999, pp. 1575
DOI: 10.1126/science.329.5999.1575-a
CREDIT: SAKAUE ET AL., CURR. BIOL. 20, 1452 (2010)
CREDIT: SAKAUE ET AL., CURR. BIOL. 20, 1452 (2010)

The blastocyst of mammalian embryos includes an inner cell mass, which goes on to form the embryo proper, and the trophectoderm layer, which forms extraembryonic tissues, such as the placenta. In normal development, DNA methylation is crucial, but these modifications are erased in the zygote and reestablished during subsequent rounds of cell division. Recent work in mice showed that embryonic stem cells (derived from the inner cell mass) do not need the three DNA methyltransferases (Dnmt1, Dnmt3a, and Dnmt3b). Sakaue et al. now demonstrate that a differentiated cell type of the extraembryonic lineage can also dispense with them. When methyltransferase-deficient mouse embryos were generated via nuclear transfer technology, cells appeared normal up to the blastocyst stage (top). Later, cell death was seen in embryonic cell lineages, whereas typical extraembryonic lineages (green just above) were observed. This finding indicates that the mouse epiblast lineage can be specified without DNA methylation but that these cells do not persist; in contrast, extraembryonic cells do differentiate, and trophoblastic stem cells can be established in the absence of zygotic DNA methylation. At this point, the reason for this divergent requirement in these lineages for epigenetic modification is unknown.

Curr. Biol. 20, 1452 (2010).

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