The zinc-finger protein Zelda is a key activator of the early zygotic genome in Drosophila

In all animals, the initial events of embryogenesis are controlled by maternal gene products that are deposited into the developing oocyte. At some point after fertilization, control of embryogenesis is transferred to the zygotic genome in a process called the maternal to zygotic transition (MZT). During this time many maternal RNAs are degraded and transcription of zygotic RNAs ensues1. A longstanding question has been, what factors regulate these events? The recent findings that microRNAs2,3 and Smaugs4 mediate maternal transcript degradation have shed new light on this aspect of the problem. However, the transcription factor(s) that activate the zygotic genome remain elusive. The discovery that many of the early transcribed genes in Drosophila share a cis-regulatory heptamer motif, CAGGTAG and related sequences5,6, collectively referred to as TAGteam sites5 brought up the possibility that a dedicated transcription factor could interact with these sites to activate transcription. Here we report that the zinc-finger protein, Zelda (Zld; Zinc-finger early Drosophila activator), binds specifically to these sites, and is capable of activating transcription in transient transfection assays. Mutant embryos lacking zld are defective in cellular blastoderm formation, and fail to activate many genes essential for cellularization, sex determination, and pattern formation. Global expression profiling confirmed that Zld plays a key role in the activation of the early zygotic genome, and suggests that Zld may also regulate maternal RNA degradation during the MZT.