Fate-changing transcription factors (TFs) scan chromatin to initiate new genetic programs during cell differentiation and reprogramming. Yet the protein structure domains that allow TFs to target nucleosomal DNA remain unexplored. We screened diverse TFs for binding to nucleosomes containing motif-enriched sequences targeted by pioneer factors in vivo.
View Article and Find Full Text PDFReprogramming 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.
View Article and Find Full Text PDFThe original version of this Article contained an error in Fig. 4a, in which the "=" sign of the equation was inadvertently replaced with a "-" sign. This has been corrected in the PDF and HTML versions of the Article.
View Article and Find Full Text PDFFollowing fertilization, the two specified gametes must unite to create an entirely new organism. The genome is initially transcriptionally quiescent, allowing the zygote to be reprogrammed into a totipotent state. Gradually, the genome is activated through a process known as the maternal-to-zygotic transition, which enables zygotic gene products to replace the maternal supply that initiated development.
View Article and Find Full Text PDFPioneer transcription factors can engage nucleosomal DNA, which leads to local chromatin remodeling and to the establishment of transcriptional competence. However, the impact of enhancer priming by pioneer factors on the temporal control of gene expression and on mitotic memory remains unclear. Here we employ quantitative live imaging methods and mathematical modeling to test the effect of the pioneer factor Zelda on transcriptional dynamics and memory in Drosophila embryos.
View Article and Find Full Text PDFIt has been suggested that transcription factor binding is temporally dynamic, and that changes in binding determine transcriptional output. Nonetheless, this model is based on relatively few examples in which transcription factor binding has been assayed at multiple developmental stages. The essential transcription factor Grainy head (Grh) is conserved from fungi to humans, and controls epithelial development and barrier formation in numerous tissues.
View Article and Find Full Text PDFThe transition from a specified germ cell to a population of pluripotent cells occurs rapidly following fertilization. During this developmental transition, the zygotic genome is largely transcriptionally quiescent and undergoes significant chromatin remodeling. In Drosophila, the DNA-binding protein Zelda (also known as Vielfaltig) is required for this transition and for transcriptional activation of the zygotic genome.
View Article and Find Full Text PDF