分生-课件分子生物学15-regulation of transcription in eukaryotes

Regulationoftranscription

ineukaryotes真核转录的调控ThemainwaysofregulationNucleosomesandtheirmodifications

通过核小体及其修饰来调控Manyregulatorsandlargerdistances

很多调控元件及更远距离的调控Theelaborateregulatorymachineryintranscription

有精细的转录调控机制Theregulatoryelementsofbacterial,yeast,andhumangenesThecomplication

ofregulationelementsisincreasedDomainsintranscriptionfactorsDomain（结构域）：在二级结构或超二级结构的基础上形成三级结构的局部折叠区，一条多肽链在这个域范围内来回折叠，但相邻的域常被一个或两个多肽片段连结。通常由50-300个氨基酸残基组成，其特点是在三维空间可以明显区分和相对独立，并且具有一定的生物功能如结合小分子。

Motif（基序）：是结构域的亚单位，通常由2～3二级结构单位组成，一般为α螺旋、β折叠和环（loop）。DomainsintranscriptionfactorsTheyeastactivatorGal4bindsasadimertoa17bpsiteofDNADNA-bindingdomainDNA-结合结构域Transcription-activationdomain

转录激活结构域Dimerizationdomain

二聚体结构域Ligand-bindingdomain配体结合结构域有DNA结合结构域，无激活结构域，仍能与DNA结合，但不能激活转录。反之，有激活结构域，无DNA结合结构域，也不能激活转录（图略）将酵母Gal4的激活结构域与细菌的LexA蛋白的DNA结合结构域连接，可激活基因的转录DNA-BindingDomainsMostDNA-bindingdomainsfallintothreeclassesThehelix-turn-helixdomain

（螺旋-转角-螺旋结构域）Thezincfingerdomain

（锌指结构域）Thebasicdomain

（碱性结构域）Thehelix-turn-helixdomain螺旋-转角-螺旋结构域Examplesofproteinswiththehelix-turn-helixdomain

C2H2zincfingerdomain

C2H2型锌指结构域-Anantiparallelb-strandcontainsthe2cysteines-2histidinesinana-helix-Helixandstrandarecoordinatedtoazincion11

SpecificrecognitionbetweenthezincfingeranditsDNAtargetoccursinthemajorgrooveProteinThezincfingersinTFIIIAC4zincfingerdomainC4型锌指结构域Thebasicdomain碱性结构域Dimerizationdomain

（二聚体结构域）Leucinezippers（亮氨酸拉链）Helix-loop-helix（螺旋-环-螺旋结构域）Leucinezippers（亮氨酸拉链）LeucinezipperbindwithDNATheHelix-loop-helixdomain

螺旋-环-螺旋结构域COOHNH3++++HydrophobicresiduesdemerizationDNAbindingTranscription-ActivatingDomains

（转录激活结构域）MostactivatorshaveoneofthesedomainsSomehavemorethanoneAcidicdomains（酸性结构域）suchasyeastGal4with11acidicaminoacidsoutof49aminoacidsinthedomainGlutamine-richdomains（富含谷氨酰胺结构域）includeSp1having2thatare25%glutamineProline-richdomains（富含脯氨酸结构域）suchasCTFwhichhasadomainof84aminoacids,19prolineTheGAL4ProteinTheGAL4proteinisamemberofthezinc-containingfamilyofDNA-bindingproteinsItdoesnothaveazincfingerEachGAL4monomercontainsaDNA-bindingmotifwith:6cysteinesthatcoordinate2zincionsinabimetalthiolateclusterShorta-helixthatprotrudesintotheDNAmajorgrooveistherecognitionmoduleDimerizationmotifwithana-helixthatformsaparallelcoiledcoilasitinteractswiththea-helixonanotherGAL4monomer2007-5-29

Repressordomains（阻抑物结构域）TargetfortranscriptionregulationChromatinstructure染色质结构InteractionwithTFIIDthroughspecificTAFIIsInteractionwithTFIIBInteractionormodulationoftheTFIIHcomplexactivityleadingtodifferentialphosphorylationoftheCTDofRNAPolII.转录因子调节模型RegulationmodelsGlucocorticoidReceptors（糖皮质激素受体）25

Regulationbyphospharylation蛋白磷酸化调节转录因子的活性HIVTatproteinCelldetermination：myoDSwitchbetweenproliferationanddifferentiation.(A)Conditionsfavoringproliferation(aswhenthereareabundantfibroblastgrowthfactorsinthemedium)enablethecontinuedexpressionofcyclin-dependentkinase4.ThiskinaseisabletorepresstheexpressionofMyoD.(B)Conversely,onceMyoDisformed,itcansuppresscdk4throughitsactivationofthep21protein.Inthismanner,thedividingcellswillnotdifferentiateandthedifferentiatedcellswillnotdivide.Homeodomains（同源域）HomeodomainscontainDNA-bindingmotiffunctioningashelix-turn-helixmotifsArecognitionhelixfitsintotheDNAmajorgrooveandmakesspecificcontactsthereN-terminalarmnestlesintheadjacentminorgrooveEyeAntennaHeadofanormalfruitflyHeadofadevelopmentalmutantLeg突变基因使果蝇本应长触角的地方长出脚MutationofoneofAntennapediacausestheflytoformalegwheretheantennashouldbe，whichdemonstratedthattherelationbetweengeneexpressionandembryonicdevelopment。ReviewquestionsDescribethestructureoftranscriptionfactorsineukaryotes.Whatarethehelix-turn-helixdomain,zincfingersdomainandleucinezipperdomain?Howdothesteroidhormonesre