Epigenetic reprogramming in mammals.
Epigenetic marking systems confer stability of gene expression during mammalian development. Genome-wide epigenetic reprogramming occurs at stages when developmental potency of cells changes. At fertilization, the paternal genome exchanges protamines for histones, undergoes DNA demethylation, and acquires histone modifications, whereas the maternal genome appears epigenetically more static. During preimplantation development, there is passive DNA demethylation and further reorganization of histone modifications. In blastocysts, embryonic and extraembryonic lineages first show different epigenetic marks. This epigenetic reprogramming is likely to be needed for totipotency, correct initiation of embryonic gene expression, and early lineage development in the embryo. Comparative work demonstrates reprogramming in all mammalian species analysed, but the extent and timing varies, consistent with notable differences between species during preimplantation development. Parental imprinting marks originate in sperm and oocytes and are generally protected from this genome-wide reprogramming. Early primordial germ cells possess imprinting marks similar to those of somatic cells. However, rapid DNA demethylation after midgestation erases these parental imprints, in preparation for sex-specific de novo methylation during gametogenesis. Aberrant reprogramming of somatic epigenetic marks after somatic cell nuclear transfer leads to epigenetic defects in cloned embryos and stem cells. Links between epigenetic marking systems appear to be developmentally regulated contributing to plasticity. A number of activities that confer epigenetic marks are firmly established, while for those that remove marks, particularly methylation, some interesting candidates have emerged recently which need thorough testing in vivo. A mechanistic understanding of reprogramming will be crucial for medical applications of stem cell technology.
Morgan
Hugh D
HD
Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge, UK.
Santos
Fátima
F
Green
Kelly
K
Dean
Wendy
W
Reik
Wolf
W
D000818:Animals; D019070:Cell Lineage; D019175:DNA Methylation; D047108:Embryonic Development / Q000502:physiology; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D005854:Germ Cells; D006657:Histones / Q000378:metabolism; D008297:Male; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D013234:Stem Cells / Q000166:cytology
D006657:Histones