分子生物學(xué)英文版教學(xué)課件：Chapter 7 Regulation of Gene Expression in eukaryotes

Chapter7/

第7章RegulationofGeneExpressionineukaryotes7.1HistonesandTranscriptionalRegulation7.2Post-TranscriptionalRegulation7.3NuclearExport7.4RNAstability7.5Translationalcontrol7.6mRNAlocalization7.7Proteinregulation7.8Experiments真核生物基因表達調(diào)控7.1組蛋白與轉(zhuǎn)錄調(diào)控7.2轉(zhuǎn)錄后調(diào)控7.3細胞核輸出7.4RNA穩(wěn)定性7.5翻譯調(diào)控7.6mRNA定位7.7蛋白質(zhì)調(diào)控7.8實驗研究SameDNA,differentcells

相同的DNA、不同的細胞Neuralcells神經(jīng)細胞Bloodcells血液細胞Amusclecell肌肉細胞Humancells人體細胞Wearegoingtolearn…7.1HistonesandTranscriptionalRegulationHomeodomain

同源異型域Leucinezipper亮氨酸拉鏈Zincfinger

鋅指HLH螺旋-環(huán)-螺旋Histones

/組蛋白?Chapter27.1.1HistonesandDNAorganization

組蛋白與DNA組織核心組蛋白八聚體Histonescontainmanyaminoacidswithpositivecharges

組蛋白含有許多帶正電荷的氨基酸His/Lys/Arg++++++++++++Nucleosome

/核小體TheBeads-on-a-stringmodel

線珠模型~60bp~150bpThe30nmfibre

/30nm纖維LevelsofDNAorganization

DNA組織的水平Nowshowing

ChromosomePackingFile:biophoto7\LehningerPrinciplesofBiochemistry\Threedimensionalpackingofnuclearchromosome(5’)Euchromatin

andheterochromatin常染色質(zhì)和異染色質(zhì)7.1.2HistonesandTranscription

組蛋白與轉(zhuǎn)錄Structureofhistones

/組蛋白的結(jié)構(gòu)Histonetail7.1.3Covalentmodificationofhistones

組蛋白的共價修飾Acetylation

/乙?；饔肅H3——CH3—CH3Histonecode/組蛋白密碼K9K4K9K4RepressionK9K4—CH3ActivationHistonecode/組蛋白密碼K14K8—PH10K8—PH10—AcK14—PH10—AcK14K8EffectEffectEffectHistonecode/組蛋白密碼—PH10—AcK14K8EffectAcodedlock（密碼鎖）7.1.4Proteinsthatrecognizeandmodifyhistones

識別和修飾組蛋白的蛋白質(zhì)ChromatinremodelingproteinSwi/SnfcomplexSpecifictranscriptionfactorsattractvariousenzymes

特異轉(zhuǎn)錄因子吸引不同的酶Reference:KarpusasM,NolteM,BentonCB,MeierW,LipscombWN,GoelzS

Thecrystalstructureofhumaninterferonbetaat2.2-Aresolution

Proc.Natl.Acad.Sci.U.S.A.v94,p.11813-11818Description:HumanInterferon-BetaCrystalStructure.Deposition:1997/9/9

Author:KarpusasM,NolteM,LipscombWTaxonomy:HomosapiensMMDB:8039

PDB:1AU1

StructureNeighbors:VASTINF-βRegulationofINF-βgene(1/3)INF-βgeneRegulationofINF-βgene(2/3)“Thereisnotenoughroomforme.Pleasehelptopushawaythehistones.”RegulationofINF-βgene(3/3)“Thankyou.Igotit”7.2Post-TranscriptionalRegulation

轉(zhuǎn)錄后調(diào)控Chapter5Sexdeterminationoffruitflies

果蠅的性別決定AlternativesplicingoftheSxlgeneAlternativesplicingoftheSxlgeneFurtherstudyingR.F.Weaver,MolecularBiology,Chapter14Alternativepolyadenylation

/可變聚腺苷化7.3NuclearExport/細胞核輸出ExportofheatshockproteinmRNAs

熱休克蛋白mRNA的輸出Yeastcells

www.zeiss.de/C12567BE0045ACF1/ContentsWWWInte

HIV:humanimmunodeficeincy

virusHIVExportofHIVmRNAs/HIVmRNA的輸出7.4RNAstability /RNA穩(wěn)定性CommonmechanismformRNAdegradation7.4.1mRNAStabilityRegulation

byProteins

蛋白質(zhì)調(diào)控mRNA穩(wěn)定性ARE:AU-richelementUTR:untranslated

regionFunctionofProteinTTPGrowthsignalTTP:Tristetraprolin,aCCCHzincfingerproteinTransferrin

/運鐵蛋白/cas/chemistry/guo/guoresearch.html

MembranecoatedvesicleFe3+Fe3+EndosomepH~5.0Fe3+Fe3+pHtriggersFe3+releaseTransferrincycleFe3+Fe3+pH~7.4TransferrinreceptorsDiferrictransferrinCytosolRegulationoftransferrinbyaconitase

順烏頭酸酶對運鐵蛋白的調(diào)控7.4.2mRNAStabilityRegulation

bySmallRNAs

小RNA調(diào)控mRNA穩(wěn)定性RNAstabilityRegulatedbyproteinsRegulatedbysmallRNAsmiRNAsiRNARNA

interference(RNAi,

RNA干涉)RNAinterference:AprocessthatusessiRNAormiRNAtoinducedegradationofatargetmRNA.（一種siRNA或miRNA誘導(dǎo)目標(biāo)mRNA降解的過程）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:RNAi

SilencingComplex

RNAi沉默復(fù)合體

/index.htmlFile:RISC1U04.valOriginandfunctionofmiRNAOriginandfunctionofsiRNA7.5Translationalcontrol/翻譯調(diào)控Translationalcontrolmaybedividedintotwobroadcategories,globalcontrolandmRNA-specificcontrol.ThelatterisusedtocontrolthetranslationofindividualmRNAs.Bycontrast,globalcontrolisusedtoregulatethetranslationofallmRNAsinthecellindiscriminately.翻譯調(diào)控可以被分成兩大范疇：全局控制和mRNA特異性控制。后者用來控制單個mRNA的翻譯。相反，全局控制是對細胞中所有mRNA實施不加區(qū)別的調(diào)控。7.5.1GlobalControl/全局控制www.uniklinikum-giessen.de/.../res_ires.htm

Picornavirus小核糖核酸病毒Chapter6GlobalcontrolthroughphosphorylationNormalcycleattranslationinitiationGlobalcontrolthrough4E-BPGlobalcontrolthrough4E-BP7.5.2mRNA-SpecificControl

mRNA特異性控制Mechanismsoftranslationregulationalsoexistsat

targetspecificmRNAsorgroupsofmRNAs,ratherthanalltranscripts.ThisisknownasmRNA-specificcontrol,anditdependsverymuchonsequenceswithinindividualmRNAtranscripts.翻譯調(diào)控機理也存在于對特殊的目標(biāo)mRNA分子或目標(biāo)mRNA群的調(diào)控，而不僅僅用于調(diào)控所有的轉(zhuǎn)錄產(chǎn)物。這就是mRNA特異性控制，它在很大程度上依賴于單個mRNA轉(zhuǎn)錄產(chǎn)物內(nèi)部的序列。mRNAwithCPECPE:Cytoplasmic

Polyadenylation

Element

（細胞質(zhì)聚腺苷酸化元件）/.../v21/n9/full/7594434a.html

CPEB,MaskinandeIF4EFerritin

/鐵蛋白CrystalStructureOfFerritin(Tm1128)FromThermotoga

MaritimaFile:Ferritin1VLG.valFeRegulationofferritinbyaconitase

順烏頭酸酶對鐵蛋白的調(diào)控7.6mRNAlocalization/mRNA定位Regulatorymechanismsalsoexisttocontrolwhereproteinsaremade.Cellsarenotuniformmixturesofmolecules.Someproteinsareneededincertainpartsofthecell,andsomemustbeabsentfromcertainparts.Thisisespeciallytrueformorphologicallycomplexcellslikeneurons.調(diào)控機理還能用來決定在哪兒生產(chǎn)蛋白質(zhì)。細胞并不是均勻的分子混合物。某些蛋白質(zhì)需要在細胞的某些部位出現(xiàn)，而有些則一定不能出現(xiàn)在那里。在像神經(jīng)元這樣的形態(tài)極為復(fù)雜的細胞中這種情況更為明顯。ManyproteinshavenosignalsManyproteinscontainsignalsthatcausethemtolocalizetospecificareasaftertranslation.However,manyotherproteinsdonotcontainsuchsignals.Theirlocalizationdependsto