Mechanisms of maternal intergenerational epigenetic inheritance

Mammalian embryos are formed by fusion of eggs and sperm. Here we provide an integrated overview of the major dynamic changes in transcriptional processes, chromatin composition and 3D organization which the maternal and paternal genomes undergo during oocyte and early embryonic development in mice. We derive mechanistic insights into molecular hierarchies and crosstalk between the various chromatin-associated processes that define three distinct types of maternal epigenetic memory states in oocytes to support pre-implantation and post-implantation development. Firstly, H3 lysine 4 trimethylation (H3K4me3) licenses early embryonic transcription by counteracting repressive H3K9 methylation. Secondly, an extensive interplay between transcription, H3K36me3 and H3K4 demethylation drives de novo DNA methylation required for embryogenesis. Thirdly, maternally inherited Polycomb-mediated H3K27me3 is a potent regulator of post-implantation development. Additionally, Polycomb Group proteins and H3K4me3 regulate 3D organization in oocytes and embryos.