Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites.

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.

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Epigenetic reprogramming in mammals

DNA methylation is one of the best-characterized epigenetic modifications and has been implicated in numerous biological processes, including transposable element silencing, genomic imprinting and X chromosome inactivation. Compared with other epigenetic modifications, DNA methylation is thought to be relatively stable. Despite its role in long-term silencing, DNA methylation is more dynamic than originally thought as active DNA demethylation has been observed during specific stages of development. In the past decade, many enzymes have been proposed to carry out active DNA demethylation and growing evidence suggests that, depending on the context, this process may be achieved by multiple mechanisms. Insight into how DNA methylation is dynamically regulated will broaden our understanding of epigenetic regulation and have great implications in somatic cell reprogramming and regenerative medicine.

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Active DNA demethylation: many roads lead to Rome

https://www.childrenshospital.org/~/media/research-and-innovation/research-labs/shi-lab/jmjd2-whetstine-et-al.ashx?la=en

Reversal of Histone Lysine Trimethylation by the JMJD2 Family of Histone Demethylases

Dynamic chromatin modifications characterise the first cell cycle in mouse embryos.

We show that methylated lysine 9 of histone H3 (Me9H3) is a marker of heterochromatin in divergent animal species. It localises to both constitutive and facultative heterochromatin and replicates late in S-phase of the cell cycle. Significantly, Me9H3 is enriched in the inactive mammalian X chromosome (Xi) in female cells, as well as in the XY body during meiosis in the male, and forms a G-band pattern along the arms of the autosomes. Me9H3 is a constituent of imprinted chromosomes that are repressed. The paternal and maternal pronuclei in one-cell mouse embryos show a striking non-equivalence in Me9H3: the paternal pronucleus contains no immunocytologically detectable Me9H3. The levels of Me9H3 on the parental chromosomes only become equivalent after the two-cell stage. Finally, we provide evidence that Me9H3 is neither necessary nor sufficient for localisation of heterochromatin protein 1 (HP1) to chromosomal DNA.

Rebecca Aucott

Papers

Heterochromatin, HP1 and methylation at lysine 9 of histone H3 in animals.