Swinstead Erin E, Paakinaho Ville, Presman Diego M, Hager Gordon L
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, Bethesda, MD, USA.
Bioessays. 2016 Nov;38(11):1150-1157. doi: 10.1002/bies.201600137. Epub 2016 Sep 16.
Transcription factor (TF) signaling regulates gene transcription and requires a complex network of proteins. This network includes co-activators, co-repressors, multiple TFs, histone-modifying complexes, and the basal transcription machinery. It has been widely appreciated that pioneer factors, such as FoxA1 and GATA1, play an important role in opening closed chromatin regions, thereby allowing binding of a secondary factor. In this review we will focus on a newly proposed model wherein multiple TFs, such as steroid receptors (SRs), can function in a pioneering role. This model, termed dynamic assisted loading, integrates data from widely divergent methodologies, including genome wide ChIP-Seq, digital genomic footprinting, DHS-Seq, live cell protein dynamics, and biochemical studies of ATP-dependent remodeling complexes, to present a real time view of TF chromatin interactions. Under this view, many TFs can act as initiating factors for chromatin landscape programming. Furthermore, enhancer and promoter states are more accurately described as energy-dependent, non-equilibrium steady states.
转录因子(TF)信号传导调节基因转录,需要一个复杂的蛋白质网络。该网络包括共激活因子、共抑制因子、多种转录因子、组蛋白修饰复合物和基础转录机制。人们普遍认识到,先驱因子,如叉头框蛋白A1(FoxA1)和GATA结合蛋白1(GATA1),在打开封闭染色质区域中起重要作用,从而允许二级因子结合。在这篇综述中,我们将重点关注一种新提出的模型,其中多种转录因子,如类固醇受体(SRs),可以发挥先驱作用。这个被称为动态辅助加载的模型整合了来自广泛不同方法的数据,包括全基因组染色质免疫沉淀测序(ChIP-Seq)、数字基因组足迹分析、DNase I超敏感位点测序(DHS-Seq)、活细胞蛋白质动力学以及ATP依赖性重塑复合物的生化研究,以呈现转录因子与染色质相互作用的实时视图。按照这种观点,许多转录因子可以作为染色质格局编程的起始因子。此外,增强子和启动子状态更准确地描述为能量依赖的非平衡稳态。