Pluto Bioinformatics

GSE112832: SETD2 regulates the maternal epigenome and embryonic development [RNA-seq]

Bulk RNA sequencing

Mammalian oocyte epigenome plays critical roles in gametogenesis and embryogenesis. Yet, how it is established remains elusive. Here, we report that SETD2, an H3K36me3 methyltransferase, is a crucial regulator of the mouse oocyte epigenome. Setd2 deficiency leads to extensive alterations of the oocyte epigenome, including the loss of H3K36me3, failure in establishment of 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 1-cell arrest after fertilization. The preimplantation arrest is mainly due to maternal cytosolic defect, which can be largely rescued by wild-type 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 maternal epigenome that in turn controls embryonic development. SOURCE: Yunlong Xiang (xiangyunlong1987@163.com) - Tsinghua University