【正文】 原核基因表達調(diào)控 Regulation in prokaryotes Chapter 5 OUTLINE 原核基因表達調(diào)控總論 乳糖操縱子的轉(zhuǎn)錄調(diào)控 色氨酸操縱子的轉(zhuǎn)錄調(diào)控 其它操縱子 (半乳糖、阿拉伯糖 ) 翻譯水平的調(diào)控 一、基因表達的概念 gene expression ：基因轉(zhuǎn)錄及翻譯的過程。對這個過程的調(diào)節(jié)就稱為 gene regulation 。 注意： rRNA、 tRNA編碼基因轉(zhuǎn)錄合成RNA的過程也屬于基因表達。 (1) 組成性表達 (constitutive expression) 指在個體發(fā)育的任一階段都能在大多數(shù)細胞中持續(xù)進行的基因表達。其基因表達產(chǎn)物通常是對生命過程必需的或必不可少的，且較少受環(huán)境因素的影響。 (2) 適應性表達 (adaptive expression) 指環(huán)境的變化容易使其表達水平變動的一類基因表達。 二、基因表達的方式 (1) 組成性表達 指 不大受環(huán)境變動而變化的一類基因表達。 ① 某些基因在一個個體的幾乎所有細胞中持續(xù)表達，通常被稱為 管家基因 (housekeeping gene)。 ② 管家基因表達水平受環(huán)境因素影響較小，而是在個體各個生長階段的大多數(shù)、或幾乎全部組織中持續(xù)表達，或變化很小。它的表達只受啟動序列或啟動子與 RNA聚合酶相互作用的影響，而不受其他機制調(diào)節(jié)。 指環(huán)境的變化容易使其表達水平變動的一類基因表達。 ① 應環(huán)境條件變化基因表達水平增高的現(xiàn)象稱為誘導 (induction)，這類基因被稱為 可誘導的基因 (inducible gene)； ② 相反，隨環(huán)境條件變化而基因表達水平降低的現(xiàn)象稱為 阻遏 (repression)，相應的基因被稱為 可阻遏的基因 (repressible gene)。 (2) 適應性表達 誘導作用： 指一些基因在特殊的代謝物或化合物的作用下，由原來關(guān)閉的狀態(tài)變?yōu)楣ぷ鳡顟B(tài)，即在某些物質(zhì)的誘導下使基因活化。 例如： 乳糖 乳糖操縱子 （ β 半乳糖苷酶 使乳糖水解為半乳糖和葡萄糖； β半乳糖苷透過酶 使乳糖進入細菌細胞內(nèi)； β半乳糖苷乙?；D(zhuǎn)移酶 使半乳糖苷第六位碳原子乙?；?。 誘導和阻遏 阻遏作用： 一些基因平時都是開啟的，處在蛋白質(zhì)或酶的工作過程中，由于一些特殊代謝物或化合物的積累而將其關(guān)閉，阻遏了基因的表達。 例如： 色氨酸－色氨酸合成酶 。一般情況下細菌自身可以合成色氨酸，但加入色氨酸，細菌因為不需要自身合成色氨酸，因此關(guān)閉該操縱子基因。 誘導和阻遏 原核基因表達調(diào)控類型及特點 負轉(zhuǎn)錄調(diào)控 (調(diào)節(jié)基因的產(chǎn)物為阻遏蛋白 ) 正轉(zhuǎn)錄調(diào)控 (調(diào)節(jié)基因的產(chǎn)物 為激活蛋白 ) 負控誘導 (阻遏蛋白不與誘導物結(jié)合，結(jié)構(gòu)基因不轉(zhuǎn)錄 ) 負控阻遏 (阻遏蛋白與誘導物結(jié)合，結(jié)構(gòu)基因不轉(zhuǎn)錄 ) 正控誘導 (誘導物使激活蛋白處于活性狀態(tài) ) 正控阻遏 (誘導物使激活蛋白處于非活性狀態(tài) ) 原核生物的基因調(diào)控主要發(fā)生在轉(zhuǎn)錄水平 1. Gene Expression is Controlled by Regulatory Proteins (調(diào)控蛋白 ) Gene expression is very often controlled by Extracellular Signals, which are municated to genes by regulatory proteins: ?Positive regulators or activators(激活蛋白 )INCREASE the transcription ?Negative regulators or repressors(阻遏蛋白 )DECREASE or ELIMINATE the transcription 2. Gene expression is controlled at different stages ?The bulk of gene regulation takes place at the initiation of transcription. ?Some involve transcriptional elongation/termination, RNA processing, and translation of the mRNA into protein. promoter binding: many promoters are regulated by activators that help RNAP bind DNA (recruitment) and by repressors that block the binding. (1)RNAP binds many promoters weakly, activators that contain two binding sites to bind a DNA sequence and RNAP simultaneously can enhance the RNAP affinity with the promoters, and thus increases gene is called recruitment regulation (招募調(diào)控 ). (2)On the contrary, Repressors can bind to the operator inside of the promoter region, which prevents RNAP binding and the transcription of the target gene. transition to the open plex: Allostery regulation (異構(gòu)調(diào)控 ) after the RNA Polymerase Binding (1) In some cases, RNAP binds the promoters efficiently, but no spontaneous isomerization occurs to lead to the open plex, resulting in no or low transcription. (2) Some activators can bind to the closed plex, inducing conformational change in either RNAP or DNA promoter, which converts the closed plex to open plex and thus promotes the transcription. promoter escape by some repressors Repressors can work in ways: (1) blocking the promoter binding. (2) blocking the transition to the open plex. (3) blocking promoter escape. 6. Cooperative binding (recruitment) and allostery have many roles in gene regulation For example: group of regulators often bind DNA cooperatively (activators and/or repressors interact with each other and with the DNA, helping each other to bind near a gene they regulated) : ? produce sensitive switches to rapidly turn on a gene expression, ? integrate signals (some genes are activated when multiple signals are present). 弱化子對基因活性的影響 弱化子： (色氨酸、蘇氨酸、苯丙氨酸等 ) 當 操縱子 (是基因表達的協(xié)調(diào)單位，由啟動子、操縱基因及其所控制