Zygotic Genome Activation

Dr. Ellie Duan

In order to create a totipotent embryo, it is critical for the zygotic genome to be reprogrammed during early development across species.  The process of zygotic genome activation (ZGA) is essential in all metazoans but remains poorly understood. Pioneer transcription factors (TFs) are key to regulating ZGA because they can bind to nucleosomal DNA and open chromatin to promote binding of other TFs.  However, very little is known about how pioneer TFs regulate ZGA in any organism. Therefore, our research is focused on understanding the how multiple pioneer transcription factors work together to activate the zygotic genome.  

Drosophila is an excellent model for understanding ZGA because embryos develop outside the mother and ZGA occurs within 2 hours after egg laying. After 30 years of studying how the Drosophila genome is activated, only a single pioneer TF, Zelda, has been identified using both biochemical and in vivo approaches.  

In our lab, we combined diverse genomic, biochemical and computational approaches to demonstrate: 1) CLAMP (Chromatin-linked adaptor for Male-specific lethal MSL proteins) is a novel pioneer factor which binds to nucleosomal DNA, activates zygotic transcription, increases chromatin accessibility; 2) CLAMP and Zelda function interdependently at promoters; 3) When Zelda is bound at a locus but does not open chromatin, CLAMP can function redundantly to open the chromatin. Because ZGA is an essential process, it is key to have redundant TFs to protect organisms from lethality that would be caused by mutation of a single non-redundant factor.