Pugh B F
Center for Gene Regulation, Department of Biochemistry and Molecular Biology, The Pennsylvania State University, 6802, University Park, PA, USA.
Gene. 2000 Sep 5;255(1):1-14. doi: 10.1016/s0378-1119(00)00288-2.
The assembly of transcription complexes at eukaryotic promoters involves a number of distinct steps including chromatin remodeling, and recruitment of a TATA-binding protein (TBP)-containing complexes, the RNA polymerase II holoenzyme. Each of these stages is controlled by both positive and negative factors. In this review, mechanisms that regulate the interactions of TBP with promoter DNA are described. The first is autorepression, where TBP sequesters its DNA-binding surface through dimerization. Once TBP is bound to DNA, factors such as TAF(II)250 and Mot1 induce TBP to dissociate, while other factors such as NC2 and the NOT complex convert the TBP/DNA complex into an inactive state. TFIIA antagonizes these TBP repressors but may be effective only in conjunction with the recruitment of the RNA polymerase II holoenzyme by promoter-bound activators. Taken together, the ability to induce a gene may depend minimally upon the ability to remodel chromatin as well as alleviate direct repression of TBP and other components of the general transcription machinery. The magnitude by which an activated gene is expressed, and thus repeatedly transcribed, might depend in part on competition between TBP inhibitors and the holoenzyme for access to the TBP/TATA complex.
真核生物启动子处转录复合物的组装涉及多个不同步骤,包括染色质重塑以及募集含TATA结合蛋白(TBP)的复合物——RNA聚合酶II全酶。这些阶段中的每一个都受正向和负向因子的控制。在本综述中,将描述调节TBP与启动子DNA相互作用的机制。第一种是自动抑制,即TBP通过二聚化隔离其DNA结合表面。一旦TBP与DNA结合,诸如TAF(II)250和Mot1等因子会诱导TBP解离,而其他因子如NC2和NOT复合物则会将TBP/DNA复合物转变为无活性状态。TFIIA拮抗这些TBP阻遏物,但可能仅在启动子结合的激活剂募集RNA聚合酶II全酶时才有效。综上所述,诱导基因表达的能力可能最低程度地取决于重塑染色质以及减轻对TBP和一般转录机制其他组分的直接抑制的能力。一个被激活的基因表达的程度,也就是其被反复转录的程度,可能部分取决于TBP抑制剂和全酶之间竞争进入TBP/TATA复合物的情况。