分子生物学Chapter-7

Chapter7/第7章,RegulationofGeneExpressionineukaryotes7.1HistonesandTranscriptionalRegulation7.2Post-TranscriptionalRegulation7.3NuclearExport7.4RNAstability7.5Translationalcontrol7.6mRNAlocalization7.7Proteinregulation7.8Experiments,真核生物基因表达调控7.1组蛋白与转录调控7.2转录后调控7.3细胞核输出7.4RNA稳定性7.5翻译调控7.6mRNA定位7.7蛋白质调控7.8实验研究,SameDNA,differentcells相同的DNA、不同的细胞,Neuralcells神经细胞,Bloodcells血液细胞,Amusclecell肌肉细胞,Humancells人体细胞,Wearegoingtolearn,7.1HistonesandTranscriptionalRegulation,Homeodomain同源异型域,Leucinezipper亮氨酸拉链,Zincfinger锌指,HLH螺旋-环-螺旋,Histones/组蛋白,?,Chapter2,7.1.1HistonesandDNAorganization组蛋白与DNA组织,核心组蛋白,八聚体,Histonescontainmanyaminoacidswithpositivecharges组蛋白含有许多带正电荷的氨基酸,His/Lys/Arg,+,+,+,+,+,+,+,+,+,+,+,+,Nucleosome/核小体,TheBeads-on-a-stringmodel线珠模型,60bp,150bp,The30nmfibre/30nm纤维,LevelsofDNAorganizationDNA组织的水平,NowshowingChromosomePacking,File:biophoto7LehningerPrinciplesofBiochemistryThreedimensionalpackingofnuclearchromosome(5),Euchromatinandheterochromatin常染色质和异染色质,7.1.2HistonesandTranscription组蛋白与转录,Structureofhistones/组蛋白的结构,Histonetail,7.1.3Covalentmodificationofhistones组蛋白的共价修饰,Acetylation/乙酰化作用,CH3,CH3,CH3,Histonecode/组蛋白密码,K9,K4,K9,K4,Repression,K9,K4,CH3,Activation,Histonecode/组蛋白密码,K14,K8,H10,K8,H10,K14,H10,K14,K8,Effect,Effect,Effect,Histonecode/组蛋白密码,H10,K14,K8,Effect,Acodedlock（密码锁）,7.1.4Proteinsthatrecognizeandmodifyhistones识别和修饰组蛋白的蛋白质,Chromatinremodelingprotein,Swi/Snfcomplex,Specifictranscriptionfactorsattractvariousenzymes特异转录因子吸引不同的酶,Reference:KarpusasM,NolteM,BentonCB,MeierW,LipscombWN,GoelzSThecrystalstructureofhumaninterferonbetaat2.2-AresolutionProc.Natl.Acad.Sci.U.S.A.v94,p.11813-11818Description:HumanInterferon-BetaCrystalStructure.Deposition:1997/9/9Author:KarpusasM,NolteM,LipscombWTaxonomy:HomosapiensMMDB:8039PDB:1AU1StructureNeighbors:VAST,INF-,RegulationofINF-gene(1/3),INF-gene,RegulationofINF-gene(2/3),RegulationofINF-gene(3/3),7.2Post-TranscriptionalRegulation转录后调控,Chapter5,Sexdeterminationoffruitflies果蝇的性别决定,AlternativesplicingoftheSxlgene,AlternativesplicingoftheSxlgene,Furtherstudying,R.F.Weaver,MolecularBiology,Chapter14,Alternativepolyadenylation/可变聚腺苷化,7.3NuclearExport/细胞核输出,ExportofheatshockproteinmRNAs热休克蛋白mRNA的输出,Yeastcellswww.zeiss.de/C12567BE0045ACF1/ContentsWWWInte,HIV:humanimmunodeficeincyvirus,HIV,ExportofHIVmRNAs/HIVmRNA的输出,7.4RNAstability/RNA稳定性,CommonmechanismformRNAdegradation,7.4.1mRNAStabilityRegulationbyProteins蛋白质调控mRNA稳定性,ARE:AU-richelement,UTR:untranslatedregion,FunctionofProteinTTP,Growthsignal,TTP:aCCCHzincfingerprotein,Transferrin/运铁蛋白,/cas/chemistry/guo/guoresearch.html,Membranecoatedvesicle,Fe3+,Fe3+,EndosomepH5.0,Fe3+,Fe3+,pHtriggersFe3+release,Transferrincycle,Fe3+,Fe3+,pH7.4,Transferrinreceptors,Diferrictransferrin,Cytosol,Regulationoftransferrinbyaconitase顺乌头酸酶对运铁蛋白的调控,7.4.2mRNAStabilityRegulationbySmallRNAs小RNA调控mRNA稳定性,RNAstability,Regulatedbyproteins,RegulatedbysmallRNAs,miRNAsiRNA,RNAinterference(RNAi,RNA干涉),RNAinterference:AprocessthatusessiRNAormiRNAtoinducedegradationofatargetmRNA.（一种siRNA或miRNA诱导目标mRNA降解的过程）,www.english.vietnamnet.vn/./2006/10/618962/,TwoU.S.scientistswonNobelPrizeinmedicine(October4,2006)U.S.scientistsAndrewFireandCraigMellowontheNobelPrizeinphysiologyormedicineMondayfordiscoveringapowerfulwaytoturnofftheeffectofspecificgenes,openingpotentialnewpathsfordiseasetreatment.,FunctionsofsiRNAandmiRNA(1/3),FunctionsofsiRNAandmiRNA(2/3),FunctionsofsiRNAandmiRNA(3/3),RISC:RNAiSilencingComplexRNAi沉默复合体,File:RISC1U04.val,OriginandfunctionofmiRNA,OriginandfunctionofsiRNA,7.5Translationalcontrol/翻译调控,7.5.1GlobalControl/全局控制,www.uniklinikum-giessen.de/./res_ires.htm,Picornavirus小核糖核酸病毒,Chapter6,Globalcontrolthroughphosphorylation,Normalcycleattranslationinitiation,Globalcontrolthrough4E-BP,Globalcontrolthrough4E-BP,7.5.2mRNA-SpecificControlmRNA特异性控制,mRNAwithCPE,CPE:CytoplasmicPolyadenylationElement（细胞质聚腺苷酸化元件）,CPEB,MaskinandeIF4E,Ferritin/铁蛋白,CrystalStructureOfFerritin(Tm1128)FromThermotogaMaritima,File:Ferritin1VLG.val,Fe,Regulationofferritinbyaconitase顺乌头酸酶对铁蛋白的调控,7.6mRNAlocalization/mRNA定位,Manyproteinshavenosignals,Manyproteinscontainsignalsthatcausethemtolocalizetospecificareasaftertranslation.However,manyotherproteinsdonotcontainsuchsignals.TheirlocalizationdependstoagreatextentonwhereinthecelltheirmRNAistranslated.,许多蛋白质都带有信号，使它们在翻译后被定位到特定的区域中去。然而，还有许多蛋白质并不含有这样的信号。它们的定位在很大程度上依赖于它们的mRNA在哪儿进行翻译。,ThreemechanismsformRNAlocalizationmRNA定位的三种机理,Localizationof-actinmRNA-肌动蛋白mRNA的定位,Afibroblastcell,Localizationof-actinmRNA-肌动蛋白mRNA的定位,7.7Proteinregulation/蛋白质调控,7.8Experiments/实验研究,7.8.1Beads-on-a-stringStructur