The initiation of mammalian embryonic transcription: to begin at the beginning

Gamete (sperm and oocyte) genomes are transcriptionally silent until embryonic genome activation (EGA) following fertilization. EGA in humans had been thought to occur around the eight-cell stage, but recent findings suggest that it is triggered in one-cell embryos, by fertilization. Phosphorylation and other post-translational modifications during fertilization may instate transcriptionally favorable chromatin and activate oocyte-derived transcription factors (TFs) to initiate EGA. Expressed genes lay on cancer-associated pathways and their identities predict upregulation by MYC and other cancer-associated TFs. One interpretation of this is that the onset of EGA, and the somatic cell trajectory to cancer, are mechanistically related: cancer initiates epigenetically. We describe how fertilization might be linked to the initiation of EGA and involve distinctive processes recapitulated in cancer.

Automated summary

Gamete genomes are silent until embryonic genome activation (EGA) after fertilization. Recent findings suggest that EGA is triggered in one-cell embryos by fertilization. Post-translational modifications during fertilization may activate transcriptionally favorable chromatin and oocyte-derived transcription factors to initiate EGA. Cancer-associated pathways and genes upregulated by cancer-associated transcription factors suggest a mechanistic link between EGA and the trajectory to cancer.