The earliest stages of development in most metazoans are driven by maternally 
deposited proteins and mRNAs, with widespread transcriptional activation of the 
zygotic genome occurring hours after fertilization, at a period known as the 
maternal-to-zygotic transition (MZT). In Drosophila, the MZT is preceded by the 
transcription of a small number of genes that initiate sex determination, 
patterning, and other early developmental processes; and the zinc-finger protein 
Zelda (ZLD) plays a key role in their transcriptional activation. To better 
understand the mechanisms of ZLD activation and the range of its targets, we 
used chromatin immunoprecipitation coupled with high-throughput sequencing 
(ChIP-Seq) to map regions bound by ZLD before (mitotic cycle 8), during (mitotic 
cycle 13), and after (late mitotic cycle 14) the MZT. Although only a handful of 
genes are transcribed prior to mitotic cycle 10, we identified thousands of 
regions bound by ZLD in cycle 8 embryos, most of which remain bound through 
mitotic cycle 14. As expected, early ZLD-bound regions include the promoters and 
enhancers of genes transcribed at this early stage. However, we also observed 
ZLD bound at cycle 8 to the promoters of roughly a thousand genes whose first 
transcription does not occur until the MZT and to virtually all of the thousands 
of known and presumed enhancers bound at cycle 14 by transcription factors that 
regulate patterned gene activation during the MZT. The association between early 
ZLD binding and MZT activity is so strong that ZLD binding alone can be used to 
identify active promoters and regulatory sequences with high specificity and 
selectivity. This strong early association of ZLD with regions not active until 
the MZT suggests that ZLD is not only required for the earliest wave of 
transcription but also plays a major role in activating the genome at the MZT.