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Continued Activity of the Pioneer Factor Zelda Is Required to Drive Zygotic Genome Activation

McDaniel, Stephen L., Gibson, Tyler J., Schulz, Katharine N., Fernandez Garcia, Meilin, Nevil, Markus, Jain, Siddhant U., Lewis, Peter W., Zaret, Kenneth S., Harrison, Melissa M.
Molecular cell 2019 v.74 no.1 pp. 185-195.e4
DNA, Drosophila, embryogenesis, genome, nucleosomes, optogenetics, transactivators, transcriptome
Reprogramming cell fate during the first stages of embryogenesis requires that transcriptional activators gain access to the genome and remodel the zygotic transcriptome. Nonetheless, it is not clear whether the continued activity of these pioneering factors is required throughout zygotic genome activation or whether they are only required early to establish cis-regulatory regions. To address this question, we developed an optogenetic strategy to rapidly and reversibly inactivate the master regulator of genome activation in Drosophila, Zelda. Using this strategy, we demonstrate that continued Zelda activity is required throughout genome activation. We show that Zelda binds DNA in the context of nucleosomes and suggest that this allows Zelda to occupy the genome despite the rapid division cycles in the early embryo. These data identify a powerful strategy to inactivate transcription factor function during development and suggest that reprogramming in the embryo may require specific, continuous pioneering functions to activate the genome.