In a new study, Yale University researchers shed light on the molecular processes that occur following fertilization to “awaken” the new genome formed through the combination of chromosomes from the parent’s egg and sperm. Their findings were published today in Developmental Cell.
The new findings help explain how transcriptional activity and subsequent development is taken over by the embryonic genome, a topic of keen interest to developmental biologists.
Through a combination of microscopy and RNA sequencing analysis, the research team analyzed the transcription process in a zebrafish embryo, identifying two specific factors needed to activate DNA in a newly formed genome. These proteins are P300 and Brd4, which are both produced by the mother. Disruption of these two proteins prevented activation and downstream development of the embryonic genome. Reintroducing the two proteins was enough to kick-start the process.
Live cell imaging was also used to visualize the first activated gene in the zebrafish genome, known as miR-430, and trace its activation in the embryo, revealing it to be gradual and stochastic.
"These molecular factors act as a sort of molecular timer, which sets the timing of genome's awakening," said Antonio Giraldez, the Fergus F. Wallace Professor of Genetics and chair of the Department of Genetics at Yale. "Finding these key factors involved in genome activation serve as the critical first step towards our understanding of how life begins."