Abstract:

Zygotic genome activation (ZGA) marks the first transcription event in development. Deciphering key regulators of ZGA is crucial for understanding how life begins and how a totipotent embryo arises from terminally differentiated gametes. Probing these questions in mammals was long hindered by the scarce experimental materials that are available from early embryos. By developing a set of ultra-sensitive chromatin analysis technologies, we previously investigated chromatin accessibility, epigenetic modifications, 3D chromatin architecture, and RNA Pol II engagement during mammalian ZGA. These studies unveiled highly dynamic and non-canonical transcription and chromatin regulation during the maternal-to-zygotic transition. However, how ZGA is kickstarted and how the early development program is progressively driven by transcription factors (TFs) remain enigmatic. Recently, we sought to identify key TFs that act at the onset of ZGA, and those that connect ZGA to the first cell fate commitment. In this talk, I will discuss how these findings help illuminate the core transcription circuitry underlying the beginning of the life.