Tamura T, Makino Y, Kishimoto T
Department of Biology, Faculty of Science, Chiba University.
Nihon Rinsho. 1995 Apr;53(4):1033-47.
Gene expression is governed by multiple cellular processes including transcription, splicing, and translation. Among them, transcriptional regulation is the main regulatory mechanism. Transcription process can be divided into pre-initiation, initiation, elongation and termination, and transcriptional regulation is especially governed through the pre-initiation step. Eukaryotic RNA polymerase alone is not able to initiate specific transcription, but general transcription factors (GTFs) is required for this reaction. In pre-initiation step, many GTFs and RNA polymerase gather at the core promoter of a gene, and form a large initiation complex. There are another class of factors: transcription regulatory factors (TRFs) responsible for the regulation such as tissue-specific/timing-specific transcription and induction/repression of transcription. TRFs directly bind to cis-acting DNA elements which are generally referred enhancers (for activation) or silencers (for repression), and regulate the rate of formation of initiation complex. A TRFs can be divided into at most 4 domains: domains for binding to DNA, regulation of transcription, interaction to other proteins and ligand binding. A number of TRFs can be categorized into rather small numbers of families such as b-zip, Zn-finger, etc. which have a characteristic combination with functional motifs. The third class of transcription factor is referred as a mediator/coactivator, that binds to both TRFs and GTFs, and can transduce the regulatory signal from enhancer to promoter. We can describe many biological processes by a term of transcriptional regulation, such as carcinogenesis, development, morphogenesis, infection and immunity, cell growth and hormone action, etc. However, further studies on chromain/nuclear matrix structure, molecular anatomy of transcription factors, and network of transcription factors are required for understanding of the relationship between biological processes and transcriptional regulation.
基因表达受多种细胞过程调控,包括转录、剪接和翻译。其中,转录调控是主要的调控机制。转录过程可分为起始前、起始、延伸和终止阶段,转录调控尤其通过起始前阶段进行。真核生物的RNA聚合酶单独无法启动特异性转录,而是需要通用转录因子(GTFs)参与此反应。在起始前阶段,许多GTFs和RNA聚合酶聚集在基因的核心启动子处,形成一个大型起始复合物。还有另一类因子:转录调节因子(TRFs),负责组织特异性/时间特异性转录以及转录的诱导/抑制等调控。TRFs直接结合通常被称为增强子(用于激活)或沉默子(用于抑制)的顺式作用DNA元件,并调节起始复合物的形成速率。一个TRF最多可分为4个结构域:与DNA结合的结构域、转录调控结构域、与其他蛋白质相互作用的结构域和配体结合结构域。许多TRFs可归类为数量较少的家族,如b-zip、锌指等,它们具有与功能基序的特征性组合。第三类转录因子被称为中介体/共激活因子,它与TRFs和GTFs都结合,并能将调控信号从增强子传递到启动子。我们可以用转录调控这一术语来描述许多生物学过程,如致癌作用、发育、形态发生、感染与免疫、细胞生长和激素作用等。然而,为了理解生物学过程与转录调控之间的关系,还需要进一步研究染色质/核基质结构、转录因子的分子解剖学以及转录因子网络。