It 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. Drosophila melanogaster, which possess a single grainy head (grh) gene, provide an excellent system to study this conserved factor. To determine whether temporally distinct binding events allow Grh to control cell fate specification in different tissue types, we used a combination of ChIP-seq and RNA-seq to elucidate the gene regulatory network controlled by Grh during four stages of embryonic development (spanning stages 5–17) and in larval tissue. Contrary to expectations, we discovered that Grh remains bound to at least 1146 genomic loci over days of development. In contrast to this stable DNA occupancy, the subset of genes whose expression is regulated by Grh varies. Grh transitions from functioning primarily as a transcriptional repressor early in development to functioning predominantly as an activator later. Our data reveal that Grh binds to target genes well before the Grh-dependent transcriptional program commences, suggesting it sets the stage for subsequent recruitment of additional factors that execute stage-specific Grh functions.
Bibliographical noteFunding Information:
The authors thank Catherine Fox, Andy Mehle, Sophia Sdao, and members of the Harrison laboratory for useful discussions and comments on the manuscript. Fly strains carrying the grhB37 allele were kindly provided by Sarah Bray. We would also like to thank the University of Wisconsin Biotechnology Center DNA Sequencing Facility. This work was supported by a Basil O’Connor Starter Scholar Research Award #5-FY14-29 and Wisconsin Partnership Program New Investigator Award #2826 to M.M.H. T.K. is a member of the Israeli Center of Excellence (I-CORE) for Gene Regulation in Complex Human Disease (no. 41/11) and the Israeli Center of Excellence (I-CORE) for Chromatin and RNA in Gene Regulation (no. 1796/12). K.N.S. was supported by the National Institutes of Health (NIH) National Research Service Award T32 GM07215.
© 2017 by the Genetics Society of America.
- Epithelial cell fate
- Pioneer factor