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.
Highlights
During metazoan embryonic development, cell-specific patterns of gene regulation are driven by complex transcriptional networks (Bonn and Furlong, 2008; Davidson, 2006)
Grainy head remains bound to mitotic chromatin during embryogenesis Whereas many DNA-binding factors do not remain on mitotic chromosomes, some vertebrate pioneer factors are retained on chromatin through mitosis (Bellec et al, 2018; Caravaca et al, 2013; Festuccia et al, 2016, 2017; Iwafuchi-Doi, 2019; Kadauke et al, 2012; Liu et al, 2017)
Given the role of Grainy head (Grh) as a pioneer factor in larval development and the fact that its chromatin occupancy is remarkably stable through Drosophila melanogaster development (Jacobs et al, 2018; Nevil et al, 2017; Potier et al, 2014), we wanted to test whether Grh remained associated with the compacted mitotic chromosomes
Summary
Cell-specific patterns of gene regulation are driven by complex transcriptional networks (Bonn and Furlong, 2008; Davidson, 2006). Transcriptional programs are orchestrated by cis-regulatory modules, such as enhancer and promoter elements (Bonn and Furlong, 2008; Davidson, 2006; Wittkopp and Kalay, 2012). These DNA elements provide modular platforms through which the input of multiple transcription factors integrate to output precise control of gene expression (Bonn and Furlong, 2008; Wilczyński and Furlong, 2010; Zinzen et al, 2009).
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