Zelda Binding in the Early Drosophila melanogaster Embryo Marks Regions Subsequently Activated at the Maternal-to-Zygotic Transition

By Melissa M. Harrison, Xiaoyong Li, Tommy Kaplan, M. Botchan, Michael B. Eisen. 2011

347 citations recorded by the source corpus.

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.

Subfields: Genetics, Molecular Biology

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Citations in the corpus

Iterative random forests to discover predictive and stable high-order interactions (2017, background): “Zld has been previously shown to play an essential role during the maternal–zygotic transition (33, 34), and there is evidence to suggest that Zld facilitates binding to regulatory elements (35).”
Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo (2015, methodology): “To determine if Zld enabled binding of these proteins by creating open regions of chromatin, we reanalyzed a published ChIP-seq data set identifying Bcd-binding sites in both wild-type embryos and those lacking maternal zld (Xu et al. 2014).”
Modification of enhancer chromatin: what, how and why? (2013, background): “Analyses of histone modifications over 1% of the human genome conducted in the initial phase of the ENCODE project associated presence of H3K4me1 with distal enhancer regions, in contrast to H3K4me3, which is present at active promoters (Heintzman et al., 2007).”
Impacts of the ubiquitous factor Zelda on Bicoid-dependent DNA binding and transcription in Drosophila (2014, methodology): “Finally, 63 of the 66 active fragments correspond to in vivo Zld-binding peaks from previous studies, compared with only 17 of the 38 inactive fragments (Harrison et al. 2011).”
Establishment of regions of genomic activity during the Drosophila maternal to zygotic transition (2014, methodology): “, 2011), we manually removed embryos of incorrect stages by inspection under a light microscope, as previously described (Harrison et al., 2011).”