Institute for Regenerative Medicine, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, 9-131 SCTR, 3400 Civic Center Blvd., Philadelphia, PA 19104-5157, USA; Department of Biology, School of Arts and Sciences, University of Pennsylvania, 433 S University Ave, Philadelphia, PA 19104-4544, USA.
Institute for Regenerative Medicine, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, 9-131 SCTR, 3400 Civic Center Blvd., Philadelphia, PA 19104-5157, USA.
Curr Opin Struct Biol. 2022 Aug;75:102425. doi: 10.1016/j.sbi.2022.102425. Epub 2022 Jul 18.
Pioneer transcription factors are able to bind a partially exposed motif on the surface of a nucleosome, enabling the proteins to target sites in silent regions of chromatin that have been compacted by linker histone. The targeting of nucleosomal DNA by pioneer factors has been observed in vitro and in vivo, where binding can promote local nucleosome exposure that allows other transcription factors, nucleosome remodelers, and histone modifiers to engage the chromatin and elicit gene activation or further repression. Pioneer factors thereby establish new gene expression programs during cell fate changes that occur during embryonic development, regeneration, and cancer. Here, we review recent biophysical studies that reveal the structural features and strategies used by pioneer factors to accomplish nucleosome binding and the consequential changes to nucleosomes that can lead to DNA accessibility.
先驱转录因子能够结合核小体表面部分暴露的基序，使这些蛋白能够靶向由连接组蛋白压缩的染色质沉默区域中的位点。体外和体内都观察到了核小体 DNA 被先驱因子靶向，结合可以促进局部核小体暴露，从而允许其他转录因子、核小体重塑因子和组蛋白修饰因子与染色质结合并引发基因激活或进一步抑制。因此，先驱因子在胚胎发育、再生和癌症过程中细胞命运变化期间建立新的基因表达程序。在这里，我们回顾了最近的生物物理研究，这些研究揭示了先驱因子结合核小体的结构特征和策略，以及由此导致的核小体变化，从而导致 DNA 可及性。
