GSE30757
Zelda binding in the early Drosophila melanogaster embryo marks regions subsequently activated at the maternal-to-zygotic transition
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 essential developmental processes. The zinc-finger transcription factor Zelda (ZLD) plays a key role in the transcriptional activation of these earliest-expressed genes. 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 prior to (mitotic cycles 8 and 9), during (mitotic cycles 13 and early 14) 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 8-9 embryos, most of which remain bound through mitotic cycle 14. As expected, these ZLD-bound regions include the promoters and enhancers of the small subset of genes transcribed at this early stage. However we also observed ZLD bound at cycle 8-9 to the promoters of a large fraction of the several thousand genes whose first transcription does not occur until roughly an hour and four mitotic cycles later. These early ZLD-bound regions include virtually all of the thousands of known and presumed enhancers bound at cycle 14 by the 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. Overall design: Genome-wide mapping of Zelda in wild-type Drosophila melanogaster embryos prior (mitotic cycles 8-9), during (cycles 13-14), and after (late cycle 14) maternal-to-zygotic transition