Life Sciences Research for Lifelong Health

Establishing epigenetic states in gametes: imprinting and beyond

Studying oocytes unveils a hierarchy of events that pattern epigenetic information across of the genome. Top of this hierarchy is gene transcription. Transcription governs where DNA methylation is placed (Veselovska et al. 2015). In turn, the presence of DNA methylation dictates where chromatin marks such as the activating mark H3K4me3 can be deposited (Hanna et al. 2018). Such studies reveal that the chromatin states in the oocyte are distinct from those of somatic cells, possibly related to the need to prepare the genome for activation of a new gene expression programme after fertilisation.
 
Imprinted genes, which acquire different epigenetic marks in the egg and the sperm, have provided a paradigm for exploring the epigenetic patterning of the germlines. Conventionally, imprinting is conferred through gametic DNA methylation differences, but recent research has identified genes imprinted through chromatin marks. However, the processes by which epigenetic states are transmitted from the oocyte and propagated at selected genes in the embryo are still poorly understood. Nor do we understand yet why some genes retain imprinting in the placenta but not the embryo itself.  We are ascertaining just how many imprinted genes do exist in placenta and embryo and the mechanisms leading to their persistent monoallelic expression.
Distinctive epigenetic landscape in mouse oocytes

Distinctive epigenetic landscape in mouse oocytes, in which DNA methylation (black circles) becomes established over expressed genes in fully-grown germinal vesicle (GV) oocytes and the classical mark of active gene promoters, H3K4me3, atypically becomes deposited over many untranscribed regions of the genome. From Hanna, Demond & Kelsey (2018) Epigenetic regulation in development: is the mouse a good model for the human? Human Reproduction Update http://dx.doi.org/10.1093/humupd/dmy021. Original data from Hanna et al. (2018) MLL2 conveys transcription-independent H3K4 trimethylation in oocytes. Nat. Struct. Mol. Biol. http://dx.doi.org/10.1038/s41594-017-0013-5.