Book Description

During the early stages of development, the fertilized germ cells are rapidly reprogrammed to form a pluripotent embryo. This transition in cell fate is coordinated by pioneer transcription factors that have the ability to open inaccessible chromatin to allow other factors to bind and drive gene expression. As chromatin is known to pose a barrier to transcription factor binding, these unique properties of pioneer factors make them instrumental in driving gene-regulatory networks that control critical developmental transitions. Despite the ability to access closed chromatin, pioneer factors do not function the same throughout development, so it is crucial that we understand how specific cellular environments influence pioneer factor binding and activity. The pioneer transcription factor Zelda (Zld) is essential for early embryonic reprogramming in Drosophila melanogaster. Research has shown that Zld shapes the chromatin and transcriptional landscape in the early embryo, but Zld's role later in development and the mechanisms by which Zld was regulated remained unclear. Our data has demonstrated that Zld functions to maintain the undifferentiated state of a neural stem cell population in the developing larval brain. Additionally, the ability of Zld to reprogram is conserved as Zld can also reprogram in the larval neural stem cell lineage. However, Zld binding is redistributed in the larval neuroblasts from the early embryo indicating that developmental context shapes where this transcription factor can bind. We show that Zld levels have to be precisely regulated in both the brain and the early embryo as misexpression of Zld at either stage is detrimental to the animal. The protein Brain Tumor (Brat) regulates Zld levels at both stages of development and we demonstrate that in embryos lacking functional Brat, Zld is prematurely expressed. However, early Zld expression is not sufficient to precociously activate the zygotic genome. Thus, expression of a genomic activator must be coordinated with timing of the division cycles in order to properly activate the genome. Together, our data demonstrate the Zld must be tightly regulated throughout development in order to allow for rapid transitions in cell fate. Together, our studies will help us better understand the transcriptional and post-transcriptional mechanisms regulating pioneer transcription factors.