Pioneer transcription factors bind closed chromatin, overcoming nucleosomal barriers to DNA to allow other transcription factors to direct gene expression. While their place at the top of developmental gene regulatory networks is fairly well established, it is less clear whether this role is developmentally regulated - do they always direct chromatin opening or is their function stage specific? Now, Melissa Harrison and colleagues address this question by investigating the pioneer activity of Grainy head (Grh), a highly conserved transcription factor known to be required for chromatin accessibility in Drosophila eye discs and mammalian cell culture. First, the authors show that, like some vertebrate pioneer factors, Drosophila Grh stays associated with chromatin during mitosis. Surprisingly, even though maternal grh is required for normal gene expression in early embryos, it is not required to establish normal chromatin accessibility. Furthermore, zygotic expression of grh is not required for the dramatic changes in chromatin accessibility that occur during gastrulation (even though Grh binding is enriched in opened regions); even knocking out both maternal and zygotic contributions does not affect accessibility. In contrast, in later embryos, the authors find 92 genomic regions in which chromatin accessibility is dependent on Grh, similar to the role of Grh in larval eye discs . Finally, loss of Grh binding at a single site in the ladybird promoter does not change chromatin accessibility. The pioneering activity of a key transcription factor is thus temporally regulated during development, raising the question of what underlies the permissive versus restrictive contexts?
Grainy head: a context-specific pioneer
Grainy head: a context-specific pioneer. Development 1 March 2020; 147 (5): e0503. doi:
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