第6章基因表达调控

单击此处编辑母版标题样式,*,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,第,6,章 基因表达调控,(,Controlling of the Gene Expression),6.1.,概述,6.2.,基因表达调控的理论与模式,6.1.,概述,（,Introduction,）,a),原核生物对环境的适应，相关的应答,真核生物的细胞分化,组织特化,个体发育,以及环境对个体表型的影响都是,基因表达的结果,基因表达的调控涉及,RNA,转录的开,/,关，数量，选择性加工,蛋白质翻译速率，数量，加工与 降解和分泌,原核生物与真核生物基因,表达调控机制具有惊人的相似性,共同的起源与共同的分子基础,调控机理上,调控层次上,核酸分子间的互作,核酸与蛋白质分子间的互作,蛋白质分子间的互作,transcriptional level,posttranscriptional level,translational level,posttranslational level,转录水平上的调控是最为经济,灵活，又是最为重要，复杂的调控,在复杂的基因组内，确定需要基因转录的起始位点,精细调节基因表达的水平,以保证生物体对环境的适应,cis,factor&trans factor,间严格而又灵活的互作,保证,RNA polymerase,的进行式转录（不中断，准确终止）,e),生物遗传信息的概念,C,c,Genome DNA,10%;,结构基因的编码序列,triplet,codon,90%;,重复，间隔，调节序列,基因选择性表达指令,重要的遗传信息,遗传信息的两大类别,II,类；特定,DNA seq.+,特定蛋白质,/,核酸结合,基因表达的指令,gene on,/,off,I,类；,DNA seq.RNA seq.(,codon,),aa,seq.,protein phenotype (central dogma),f),遗传信息表达的方式,组成型表达（,constitutive expression,）,持家基因,Housekeeping gene,诱导型表达,（,inducible expression by signaling molecular,）,奢侈基因,Luxury gene,顺、反因子间互作方式的基因表达调控,上位显性,Epistasis,effect,6.2,基因表达调控的,理论与模式,转录水平的调控,（,transcriptional level control,）,Prok,.,操纵子,operon,逆境应答,stringent response,衰减子,attenuator,转座子,transposon,6.2.1.,操纵子调控（,Operon,control,）,(1961 Jacob.&Monod.),a),operon,concept,控制某一代谢途径的相关基因,紧密连锁地排列在一起,受同一操纵子控制,各结构基因按一定比例协调翻译,(Z:Y:A=5:2:1),具有极性突变效应,P&O,基因,(,cis,),紧密连锁,或,彼此重叠,I,基因,(trans),位点不固定,Lac,operon,I p o Z Y A,b),operon,control type,负调控,Negative&,正调控,Positive,I gene,Neg.,Pos.,i,-,or,不加入,I,基因产物,operon,on,I,+,or,加入,I,基因产物,operon,off,i,-,or,不加入,I,基因产物,operon,off,I,+,or,加入,I,基因产物,operon,on,repressor,Negative,Positive,expressor,(,apoinducer,),无辅基,诱导物,Repressor binding on O site,Operon,off,Negative,contrl,是广泛保险的机制,（自然选择使,Prok,.,获得选择优势）,Positive control,是灵活，严格，经济的调控机制,Expressor,binding front p site,意味转录效率极低,阻止转录启动,激活转录启动,c)Model,信号分子（,Signal molecular,）,be needed for both types,Add,signal mol.,Operon,on,Add,signal mol.,Operon,off,辅,阻遏物,Co-repressor,诱导物,Inducer,(inducible,operon,),(repressible,operon,),Operon,control model,negative,positive,Ind.,Rep.,active,active,inactive,inactive,cAMP,control,(universal controlling system),Lac,operon,open,but no transcripts,Glucose,Why?,Lactose,E.coli,6.2.2.,乳糖操纵子的基因表达调控,ATP,ppp,c A,cAMP,p c A,5-AMP,p c A,I(,crp,gene),(,cAMP,reccept,protein),(or,catabilite,gene activator protein),cAMPase,(-),phospho,diesterase,(+),+,Glucose,Lac.Operon,I P O,cAMP,CAP,具有广泛生理效应的正控制系统,存在于多种基因表达调控体系中,Lac,operon,expression,cAMP,(Positive-inducible),lactose,(Negative-inducible),6.2.3.,衰减子调控（,Attenuator control,）,a)discovery,E.coli,trp,synthetase,operon,(,Charles,Yanofsky,stanford,.U),Negativerepressible,operon,70-fold lower than fully,derepressed,I P O leading seq.E D C B A,trp,+,1968.,Imamato,Lab.,仅有少量,trp,时，,RANpol,启动，,但在,L.S.,处脱落，转录中断,I P,O,leading seq.E D C B A,少量,trp,+,不足以结合,O,位点,S.D.,Seq,14 amino acid leader peptide,stop,UGA,trp,E,b),trp,operon,RNA,一级结构分析,114121126134(,palindromic,seq.)with poly(U),2768 base,ORF of 14aa,140 base RNA almost binding with protein(,translable,seq.),trp,high frequency with 1/7 in 14,aa,114 121 126 134 140,27,68,Trp,1/7,不同氨基酸合成酶操纵子引导肽的,氨基酸序列,c),调控机制分析,1-2/3-4,2-3,调控机制分析,Trp(Arg,),starved,Non-starved,trp,trp,55-58-,65-68-,Arg,60-,70-,UGA,69-,79-,2-3,3-4,Rho-independent T.,Transcription be controlled by translation of short peptide coding in leading sequence,No tryptophan,Tryptophan present,d)Attenuator control,的生物学意义,原核生物细致的精细调控机制,增强原核生物对环境的适应性,当有少量,trp,存在,repressor,不足以关闭,operon,当有大量,trp,存在 少量,RNApol,通过,O,位点,只要细胞内有,trp-tRNA,trp,存在,Attenuator,就会使,RNApol,在引导区转录中断,Yanofsky,Charles.1981.,Nature.,289;751-758,通过引导区短肽的翻译过程,对,operon,转录的精细控制,I,po,L.S.E D C B A,tRNA,trp,+,trp,trp,trp-tRNA,trp,protein synthesis,Trp,synthetase,opron,