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. 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).