Broad H3K4me3 domains support oocyte genome silencing and maturation but are dispensable for repression in early embryos.

Epigenetic reprogramming and embryonic genome activation (EGA) are crucial events during early development. Establishment of distinctive broad histone H3 lysine 4 trimethylation (H3K4me3) domains in the oocyte is necessary for genome silencing, and their removal in the 2-cell embryo is crucial for EGA and development in mice. However, the stage-specific requirement for broad H3K4me3 domains is unclear. Here, we show that inducing broad H3K4me3 removal in mouse oocytes can relieve genome silencing, impair oocyte maturation timing, and may cause transcriptional reactivation in resulting parthenogenetic 1-cell embryos. We further demonstrate that broad H3K4me3 demethylation precedes EGA but, surprisingly, premature depletion in zygotes or early 2-cell embryos does not alter the transcriptional program. Our findings suggest that broad H3K4me3 domains are required for oocyte genome silencing, timely maturation and post-fertilisation silencing, but onward pre-EGA transcriptional repression is not dependent on the original mark. This work contributes to the understanding of events and mechanisms involved in genome silencing and activation in early development, providing insight into potential modes of failure that may contribute to infertility.