Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 52706, USA.
Development. 2024 Jul 1;151(13). doi: 10.1242/dev.201921. Epub 2024 Jul 3.
Development is regulated by coordinated changes in gene expression. Control of these changes in expression is largely governed by the binding of transcription factors to specific regulatory elements. However, the packaging of DNA into chromatin prevents the binding of many transcription factors. Pioneer factors overcome this barrier owing to unique properties that enable them to bind closed chromatin, promote accessibility and, in so doing, mediate binding of additional factors that activate gene expression. Because of these properties, pioneer factors act at the top of gene-regulatory networks and drive developmental transitions. Despite the ability to bind target motifs in closed chromatin, pioneer factors have cell type-specific chromatin occupancy and activity. Thus, developmental context clearly shapes pioneer-factor function. Here, we discuss this reciprocal interplay between pioneer factors and development: how pioneer factors control changes in cell fate and how cellular environment influences pioneer-factor binding and activity.
发育受基因表达协调变化的调控。这些表达变化的控制主要受转录因子与特定调节元件结合的控制。然而,DNA 包装成染色质会阻止许多转录因子的结合。先驱因子由于具有独特的特性而克服了这一障碍,使它们能够与封闭的染色质结合,促进可及性,并以此介导激活基因表达的其他因子的结合。由于这些特性,先驱因子在基因调控网络的顶端发挥作用,并推动发育转变。尽管能够结合封闭染色质中的靶基序,但先驱因子在染色质上的占据和活性具有细胞类型特异性。因此,发育背景显然塑造了先驱因子的功能。在这里,我们讨论了先驱因子与发育之间的这种相互作用:先驱因子如何控制细胞命运的变化,以及细胞环境如何影响先驱因子的结合和活性。