Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA.
Department of Biomolecular Chemistry, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53706, USA
Development. 2020 Mar 11;147(5):dev185009. doi: 10.1242/dev.185009.
The dramatic changes in gene expression required for development necessitate the establishment of 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 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.
发育所需的基因表达的巨大变化需要建立由可及染色质区域定义的调控模块。先驱转录因子具有结合封闭染色质并促进这些可及区域建立的独特性质。尽管如此,先驱转录因子在发育过程中如何协调染色质可及性的变化仍知之甚少。为了确定先驱因子的功能是内在蛋白固有的,还是先驱活性是发育调节的,我们研究了高度保守的、必需的转录因子 Grainy head (Grh)。先前的工作表明 Grh 在整个发育过程中表达,并在幼虫中是一个先驱因子。我们证明 Grh 仍然与有丝分裂染色体结合,这是其他先驱因子所共有的特性。通过在胚胎发育的三个阶段检测缺乏母体和/或合子 Grh 的胚胎中的染色质可及性,我们发现 Grh 在早期胚胎发生中不需要染色质可及性,这与它在发育后期的必需功能形成对比。我们的数据表明,Grh 的先驱活性是时间调节的,可能受到在特定发育阶段表达的其他因素的影响。