Molecular Regulation of Transcription Initiation

本研究利用大肠杆菌sigma 70 RNA聚合酶和乳糖（lac）操纵子启动子模型系统，研究分解代谢激活蛋白CAP对基因的正调控作用。CAP被认为通过与RNA聚合酶的直接相互作用激活转录。这种相互作用的一个结果可能是刺激RNA聚合酶和特定上游DNA序列之间的相互作用。候选（-40区）DNA序列在lac启动子的CAP激活中的作用将通过化学干扰和位点特异性突变研究来研究。此外，在没有CAP的情况下，将研究这些上游序列对lacP表达的可能限制作用。基因表达的第一个事件是RNA合成或转录的起始。这个多步骤的过程涉及RNA聚合酶与称为启动子的特定DNA序列的相互作用。启动子DNA序列决定了非调控RNA合成的起始位点和频率。本研究将详细探讨细菌调控蛋白CAP如何促进RNA聚合酶与细菌启动子lac的特异性相互作用，从而激活lac基因的转录。这个CAP-lac系统是理解转录激活蛋白的一个通用模型，已知转录激活蛋白调节基因表达超过25年。* * *

9419784 Reznikoff This research uses Escherichia coli sigma 70 RNA polymerase and lactose (lac) operon promoter model system to study positive gene regulation by catabolite activator protein CAP. CAP is thought to activate transcription by direct interaction with RNA polymerase. One consequence of this interaction may be to stimulate an interaction between RNA polymerase and specific upstream DNA sequences. The role of candidate (-40 region) DNA sequences in the CAP activation of the lac promoter will be investigated through chemical interference and site-specific mutation studies. In addition, the possible limiting effect of these upstream sequences on lacP expression in the absence of CAP will be examined. %%% The first event in gene expression is the initiation of RNA synthesis or transcription. This multistep process involves the interaction of the enzyme RNA polymerase with specific DNA sequences called promoters. The promoter DNA sequence determines the start site and frequency of unregulated RNA synthesis. This research will investigate in detail how the bacterial regulatory protein CAP facilitates the specific interaction of RNA polymerase with the bacterial promoter lac to activate transcription of the lac genes. This CAP-lac system is a general model for understanding transcriptional activator proteins, which have been known to regulate gene expression for over 25 years. ***