GSE126920
DPPA2 and DPPA4 are necessary to establish a 2C-like state in mouse embryonic stem cells [RNA-seq]
After fertilization of the transcriptionally silent oocyte, expression from both parental chromosomes is launched through so-called zygotic genome activation (ZGA), occurring in the mouse at the 2-cell (2C) stage. Amongst the first elements to be transcribed are the Dux gene, the product of which secondarily induces a wide array of ZGA genes, and a subset of evolutionary recent LINE-1 retrotransposons, which regulate chromatin accessibility in the early embryo. The maternally-inherited factors that activate Dux and LINE-1 transcription have so far remained unknown. Mouse embryonic stem cells (mESCs) recapitulate some aspects of ZGA in culture, owing to their ability to cycle through a 2C-like stage where Dux, its target genes and LINE-1 integrants are expressed. Here we identify the paralog proteins DPPA2 and DPPA4 as necessary for activation of Dux and LINE-1 expression in mESCs. Since their encoding RNAs are maternally transmitted to the zygote, it is likely that these factors are important upstream mediators of murine ZGA. Overall design: RNA sequencing analysis for mESC depleted of endogenous DPPA2 or DPPA4, and DPPA4 KO cells overexpressing ectopically full-length DPPA4 (ENSMUST00000096045) or a truncated version of the protein (ENSMUST00000050705).