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

Abstract

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). Prior work established that Grh is expressed throughout Drosophila development and is a pioneer factor in the larva. We demonstrated that Grh remains bound to mitotic chromosomes, a property shared with other pioneer factors. By assaying chromatin accessibility in embryos lacking maternal and/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 likely influenced by additional factors expressed at a given developmental stage.

GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo

“…DESeq2 with an adjusted p-value < 0.05 and a fold change > 2 as thresholds for differential accessibility. Previously published ATAC-seq datasets (Hannon et al 2017), GSE86966; (Blythe and Wieschaus 2016), GSE83851; (Nevil et al 2020), GSE137075. were re-analyzed in parallel with ATAC-seq data from this study to ensure identical processing of data sets.…”

“…2016. ATAC-seq data for stage 5 embryos is fromNevil et al 2020. Region highlighted in green indicates the GAF-dependent, GAFbound Ubx promoter.…”

Cell-type-specific chromatin occupancy by the pioneer factor Zelda drives key developmental transitions inDrosophila

“…This correlation between Zld binding and open chromatin was similar to the previously reported association between Zld-bound regions and chromatin accessibility in the early embryo (Harrison et al, 2011). To better understand this relationship between accessibility and Zld binding, we used recently published ATAC-seq data generated in stage 5 embryos (Nevil et al, 2020) to allow us to compare accessibility and Zld binding in both the embryo and type II neuroblasts. This analysis showed that while Zld-bound loci and regions of open chromatin differ between the two cell types, there is a correlation between binding and accessibility in both (Figure 5A, Figure S5C).…”

Alternate Grainy head isoforms regulateDrosophilamidgut intestinal stem cell differentiation

“…This was later supported by Jacobs et al 2018 (Blastyak et al, 2006, Tuckfield et al, 2002 further illustrating the ability of Grh to recruit co-factors to confer its activator or repressive functions. Grh's pioneer factor activity appears to be regulated temporally with Grh pioneer factor activity required during late embryonic development but not during early embryonic development (Nevil et al, 2020), thus whether Grh is acting as a pioneer factor or directly activating or repressing genes in the intestine requires further investigation.…”