Development and differentiation are driven by coordinated changes in gene expression. To better understand how these processes can be regulated by broadly expressed transcription factors, we are elucidating the gene regulatory network controlled by the highly conserved transcription factor Grainy head. Grainy head orthologs are found in organisms ranging from yeast to humans and are essential for development in both flies and mice, where Grainy head is required for epithelial morphogenesis and wound healing. In flies, additional roles have been demonstrated for regulation of neural stem cell identity. Our studies will explain how a transcription factor with known roles in both the activation and repression of gene expression can control conserved processes during embryonic development in both mammals and insects.
Gene ontology network relating putative Grainyhead target genes. Network map of Grainyhead target genes generated in Cytoscape (Shannon et al. Genome Res 2003).
Nevil, M., Gibson, T.J., Bartolutti, C., Ayengar, A., and Harrison, M.M. (2020). Establishment of chromatin accessibility by the conserved transcription factor Grainy head is developmentally regulated. Development. 147:dev185009.
Reese, R.M., Harrison, M.M., and Alarid, E.T. (2019). Grainyhead-like protein 2: The emerging role in hormone-dependent cancers and epigenetics. Endocrinology 160: 1275-1288.
Nevil, M., Bondra, E. R., Schulz, K. N., Kaplan, T., and Harrison, M. M. (2017) Stable Binding of the Conserved Transcription Factor Grainy Head to Its Target Genes Throughout Drosophila melanogaster Development. Genetics. 205:605-620.
Harrison, M.M., Botchan, M.R. and T.W. Cline. (2010) Grainyhead and Zelda compete for binding to the promoters of the earliest-expressed Drosophila genes. Dev Biol. 345: 248-255.