Journal
EMBO REPORTS
Volume 20, Issue 5, Pages -Publisher
WILEY
DOI: 10.15252/embr.201847382
Keywords
DPPA2; DPPA4; DUX; LINE-1; zygotic genome activation
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Funding
- Swiss National Science Foundation
- Gebert-Ruf Foundation
- FP7 MC-ITN INGENIUM [290123]
- European Research Council [ERC 694658]
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After fertilization of the transcriptionally silent oocyte, expression from both parental chromosomes is launched through zygotic genome activation (ZGA), occurring in the mouse at the 2-cell (2C) stage. Among the first elements to be transcribed are the Dux gene, the product of which induces a wide array of ZGA genes, and a subset of evolutionary recent LINE-1 retrotransposons that 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 when Dux, its target genes, and LINE-1 integrants are expressed. Here, we identify the paralog proteins DPPA2 and DPPA4 as necessary for the 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.
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