GSE112833
SETD2 regulates the maternal epigenome, genomic imprinting and embryonic development [Bisulfite-seq]
The oocyte epigenome plays critical roles in mammalian gametogenesis and embryogenesis. Yet, how it is established remains elusive. Here, we report that histone-lysine N-methyltransferase SETD2, an H3K36me3 methyltransferase, is a crucial regulator of the mouse oocyte epigenome. Deficiency in Setd2 leads to extensive alterations of the oocyte epigenome, including the loss of H3K36me3, failure in establishing the correct DNA methylome, invasion of H3K4me3 and H3K27me3 into former H3K36me3 territories and aberrant acquisition of H3K4me3 at imprinting control regions instead of DNA methylation. Importantly, maternal depletion of SETD2 results in oocyte maturation defects and subsequent one-cell arrest after fertilization. The preimplantation arrest is mainly due to a maternal cytosolic defect, since it can be largely rescued by normal oocyte cytosol. However, chromatin defects, including aberrant imprinting, persist in these embryos, leading to embryonic lethality after implantation. Thus, these data identify SETD2 as a crucial player in establishing the maternal epigenome that in turn controls embryonic development. Overall design: Mouse GO_P7, GO_P10, GO_P14, FGO, MII oocyte, zygote, late 2-cell, 8-cell and ICM from E3.5 blastocyst were obtained and performed STAR ChIP-seq to determine the H3K36me3 distribution. FGO in Dnmt3L KO mice and Setd2 maternal KO mice were collected and conducted STAR ChIP-seq, STEM-seq and RNA-seq to explore the cross talk between histone modifications. STAR ChIP-seq and RNA-seq were performed in Setd2 maternal KO zygote to test if abnormal H3K4me3 and transcription can be inherited in mutant embryo. GO = growing oocyte FGO = full grown oocyte