Epigenetic reprogramming in mammals

Abstract

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.

Nutritional developmental epigenomics: immediate and long-lasting effects

“…Gastrulation, i.e. the formation and differentiation of the three germ layers, a crucial switch point in Proceedings of the Nutrition Society ontogeny with far-reaching consequences for pre-and postnatal development of all cells, tissues and organs (28,29) , takes place during early pregnancy.…”

Specific hypermethylation of LINE-1 elements during abnormal overgrowth and differentiation of human placenta

“…Most PHMs originate from dispermic fertilization (Zaragoza et al, 2000). In humans and other mammals the paternal pronucleus is actively demethylated at zygote formation (Young and Beaujean, 2004;Morgan et al, 2005). Experimental alterations of the zygote epigenome have provided a link between epigenetic marks and further zygote (Tavassoli and Devilee, 2003).…”

“…Immunohistochemistry using anti 5-methylcytosine antibodies was carried out as described previously (Ghabreau et al, 2004). Specific hypermethylation of LINE-1 elements D Perrin et al development (Morgan et al, 2005). Therefore, abnormal reprogramming at the stage of triploid zygote formation might be associated with these DNA methylation changes.…”

“…On fertilization, active demethylation is coupled with extensive reorganization of the histone modification patterns (Morgan et al, 2005); therefore, we investigated this issue in human triploid embryos. All three pronuclei showed abundant staining with anti-acetylated histones H4 and H3, anti-dimethyl-histone H3 (Lys4) and antitri-methyl-histone H3 (Lys9) (Supplementary Figure 7S), indicating that pronuclei were well decondensed at this stage and both types of histone modifications (acetylation and methylation) are thus shown to take place in these triploid zygotes.…”

Asymétrie des génomes parentaux

“…Une vague de déméthylation permettant la reprogrammation des génomes parentaux se produit dans un deuxième temps : le génome paternel subit dès le stade zygote une déméthylation globale, rapide et active. Il faut noter que cette déméthylation épargne les régions ICR et certaines autres séquences comme les séquences satellites ou celles des rétrotransposons [16]. Les facteurs impliqués dans cet effacement de la méthy-lation de l'ADN sont inconnus à ce jour.…”