Establishment of chromatin accessibility by the conserved transcription factor Grainy head is developmentally regulated

The dramatic changes in gene expression required for development necessitate the establishment of cis- regulatory modules defined by regions of accessible chromatin. Pioneer transcription factors have the unique property of binding closed chromatin and facilitating the establishment of these accessible regions. Nonetheless, much of how pioneer transcription factors coordinate changes in chromatin accessibility during development remains unknown. To determine whether pioneer-factor function is intrinsic to the protein or whether pioneering activity is developmentally modulated, we studied the highly conserved, essential transcription factor, Grainy head (Grh). Grh is expressed throughout Drosophila development and functions as a pioneer factor in the larvae. We demonstrated that Grh remains bound to condensed mitotic chromosomes, a property shared with other pioneer factors. By assaying chromatin accessibility in embryos lacking either maternal or zygotic Grh at three stages of development, we discovered that Grh is not required for chromatin accessibility in early embryogenesis, in contrast to its essential functions later in development. Our data reveal that the pioneering activity of Grh is temporally regulated and is likely influenced by additional factors expressed at a given developmental stage.