Cell-type-specific chromatin occupancy by the pioneer factor Zelda drives key developmental transitions in Drosophila

Elizabeth D. Larson, Hideyuki Komori, Tyler J. Gibson, Cyrina M. Ostgaard, Danielle C. Hamm, Jack M. Schnell, Cheng-Yu Lee () and Melissa M. Harrison ()
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Elizabeth D. Larson: University of Wisconsin School of Medicine and Public Health
Hideyuki Komori: University of Michigan
Tyler J. Gibson: University of Wisconsin School of Medicine and Public Health
Cyrina M. Ostgaard: University of Michigan Medical School
Danielle C. Hamm: University of Wisconsin School of Medicine and Public Health
Jack M. Schnell: University of Wisconsin School of Medicine and Public Health
Cheng-Yu Lee: University of Michigan Medical School
Melissa M. Harrison: University of Wisconsin School of Medicine and Public Health

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract During Drosophila embryogenesis, the essential pioneer factor Zelda defines hundreds of cis-regulatory regions and in doing so reprograms the zygotic transcriptome. While Zelda is essential later in development, it is unclear how the ability of Zelda to define cis-regulatory regions is shaped by cell-type-specific chromatin architecture. Asymmetric division of neural stem cells (neuroblasts) in the fly brain provide an excellent paradigm for investigating the cell-type-specific functions of this pioneer factor. We show that Zelda synergistically functions with Notch to maintain neuroblasts in an undifferentiated state. Zelda misexpression reprograms progenitor cells to neuroblasts, but this capacity is limited by transcriptional repressors critical for progenitor commitment. Zelda genomic occupancy in neuroblasts is reorganized as compared to the embryo, and this reorganization is correlated with differences in chromatin accessibility and cofactor availability. We propose that Zelda regulates essential transitions in the neuroblasts and embryo through a shared gene-regulatory network driven by cell-type-specific enhancers.

Date: 2021
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DOI: 10.1038/s41467-021-27506-y

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