Frietze Seth, Farnham Peggy J
Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles, CA, 90033, USA,
Subcell Biochem. 2011;52:261-77. doi: 10.1007/978-90-481-9069-0_12.
The last decade has seen an incredible breakthrough in technologies that allow histones, transcription factors (TFs), and RNA polymerases to be precisely mapped throughout the genome. From this research, it is clear that there is a complex interaction between the chromatin landscape and the general transcriptional machinery and that the dynamic control of this interface is central to gene regulation. However, the chromatin remodeling enzymes and general TFs cannot, on their own, recognize and stably bind to promoter or enhancer regions. Rather, they are recruited to cis regulatory regions through interaction with site-specific DNA binding TFs and/or proteins that recognize epigenetic marks such as methylated cytosines or specifically modified amino acids in histones. These "recruitment" factors are modular in structure, reflecting their ability to interact with the genome via one region of the protein and to simultaneously bind to other regulatory proteins via "effector" domains. In this chapter, we provide examples of common effector domains that can function in transcriptional regulation via their ability to (a) interact with the basal transcriptional machinery and general co-activators, (b) interact with other TFs to allow cooperative binding, and (c) directly or indirectly recruit histone and chromatin modifying enzymes.
在过去十年中,技术取得了令人难以置信的突破,使得组蛋白、转录因子(TFs)和RNA聚合酶能够在整个基因组中被精确绘制。从这项研究中可以清楚地看出,染色质景观与一般转录机制之间存在复杂的相互作用,并且这种界面的动态控制对于基因调控至关重要。然而,染色质重塑酶和一般转录因子自身无法识别并稳定结合到启动子或增强子区域。相反,它们是通过与位点特异性DNA结合转录因子和/或识别表观遗传标记(如甲基化胞嘧啶或组蛋白中特定修饰氨基酸)的蛋白质相互作用,被招募到顺式调控区域的。这些“招募”因子在结构上是模块化的,这反映了它们通过蛋白质的一个区域与基因组相互作用,并同时通过“效应器”结构域与其他调控蛋白结合的能力。在本章中,我们提供了一些常见效应器结构域的例子,这些结构域可以通过以下能力在转录调控中发挥作用:(a)与基础转录机制和一般共激活因子相互作用;(b)与其他转录因子相互作用以实现协同结合;(c)直接或间接招募组蛋白和染色质修饰酶。