Liu Zhijie, Hu Qidong, Rosenfeld Michael G
Howard Hughes Medical Institute, Department of Medicine, University of California, La Jolla, San Diego, CA, USA,
Subcell Biochem. 2014;70:203-25. doi: 10.1007/978-94-017-9050-5_10.
In the past several decades, intensive research in this field has uncovered a surprising number of regulatory factors and their associated enzymatic properties to reveal the network of complexes that function in activation and repression of the transcriptional programs mediated by nuclear receptors (NR). These factors and their associated complexes have been extensively characterized both biochemically and functionally [34, 87, 94]. Several principles have emerged: (1) It is widely recognized that ligand-dependent cofactor complexes mediating repression and activation exhibit ligand-dependent exchange. (2) These complexes mediate modifications of chromatin structure consequent to their binding at regulatory elements, particularly at promoter and enhancer Enhancer sites. (3) The concept about the rapid exchange of coregulatory complexes at regulatory sites has been suggested [88]. Key questions in the NR field have included: (a) What are the cofactors and exchange complexes used to mediate the ligand and signaling network-dependent switches in gene regulation programs; (b) Do long non-coding RNAs (lncRNAs) serve as regulatory "factors" for ligand-dependent gene programs, and do enhancers actually regulate transcription units encoding enhancer Enhancer non-coding RNAs (eRNAs) Enhancer RNA that might have functional significance; (c) What is the relationship between DNA damage repair machinery and transcriptional machinery? (d) Do Retinoic Acid Receptors (RAR) also regulate Pol III-dependent, non-coding repeat transcriptional units in stem cells? and (e) How have new technologies such as deep sequencing altered our ability to investigate transcriptional regulatory mechanisms utilized by NRs?
在过去几十年里，该领域的深入研究发现了数量惊人的调控因子及其相关酶特性，揭示了在核受体（NR）介导的转录程序激活和抑制中发挥作用的复合物网络。这些因子及其相关复合物已在生物化学和功能方面得到广泛表征[34, 87, 94]。已出现几个原则：（1）广泛认为介导抑制和激活的配体依赖性辅因子复合物表现出配体依赖性交换。（2）这些复合物在结合调控元件，特别是启动子和增强子位点后，介导染色质结构的修饰。（3）有人提出了关于共调节复合物在调控位点快速交换的概念[88]。NR领域的关键问题包括：（a）用于介导基因调控程序中配体和信号网络依赖性转换的辅因子和交换复合物是什么；（b）长链非编码RNA（lncRNA）是否作为配体依赖性基因程序的调控“因子”，增强子是否实际上调控编码可能具有功能意义的增强子RNA（eRNA）的转录单位；（c）DNA损伤修复机制与转录机制之间的关系是什么；（d）维甲酸受体（RAR）是否也调控干细胞中依赖于Pol III的非编码重复转录单位；以及（e）深度测序等新技术如何改变了我们研究NR利用的转录调控机制的能力？
