Deciphering transcription activity of mammalian early embryos unveils on/off of zygotic genome activation by protein translation/degradation.

Quantification of transcription activities in mammalian preimplantation embryos is challenging due to a huge amount of maternally stored transcripts and paucity of research materials. Here, we investigate genome-wide transcription activities of mouse and human preimplantation embryos by quantifying elongating RNA polymerase II. Two transcriptional waves are identified in early mouse embryos, with summits at the 2-cell and 8-cell stages. Gene collections with different expression patterns are obtained, with genes mainly transcribed at the mouse early/late 2-cell stage designated as zygotic genome activation-early/late 2-cell (ZGA-E2C/L2C). ZGA-E2C genes are short and have low promoter CpG density. Protein translation/degradation not only regulates transcription activity through stepwise orchestration of histone modifications, transcriptional initiation, and elongation in early mouse embryos but also controls on/off switching of ZGA-E2C/L2C genes in maternal aged mouse embryos. Genes mainly transcribed at the mouse 2-cell stage can also be transcribed as early as the human 2-cell stage.