DNA methylation functions as cellular memory beyond generations of cells and is involved in many biological processes. Because of its relatively stable nature compared with the transcriptome, the DNA methylation profile of cells can also be used to evaluate developmental similarity and cellular phenotypes. Recent insights into 5-hydroxymethylcytosine have started to reshape our view of the epigenetic regulation of mammalian development. Both global DNA meth-ylation and hydroxymethylation levels change dynamically during preimplantation embryogenesis. It is known that DNA methylation plays an essential role in embryonic cell fate restriction, whereas its role in trophoblast development requires further research. Two distinct blastocyst-derived stem cell lines, embryonic stem (ES) cells and trophoblast stem (TS) cells, are used to study the epigenetic mechanisms underlying cell lineage maintenance and the regulation of cell differentiation. Such studies will allow us to understand the details of the epigenetic landscape of trophoblast development, which should offer valuable information for managing pregnancy-related diseases in humans.
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