RegulationofGeneExpression.Whatarethe“goals”ofgeneexpression?Prokaryotes:torespondtochangesintheenvironmentEukaryotes:developmentMaintenanceofdifferentcelltypesLossofcontrolcanbedisastrous.Bacteriaregulatetranscription:operonsFeedbackinhibitionbyendproductofpathwayOperon:expressionofgenesforenzymes.Whatisanoperon?Arepressibleoperon.Lacoperonisinducible.RepressibleandinducibleoperonsRepressibleRepressordoesnotbindoperatorunlessitinteractswithco-repressorBiosyntheticpathwaysInducibleRepressorisboundtooperatorunlessmoleculetobemetabolizedispresent(inducer)CatabolicpathwaysWhenrepressorisboundtooperator,genesarenotexpressed(operonisturnedoff).PositivegeneregulationcAMPaccumulateswhenglucoseisscarceCellwilluseglucosepreferentially.Whichgenesareexpressedwhen?UnicellularorganismEnvironmentalsignalsGenerallytranscriptionisregulatedMulticellularorganismDevelopmentCellspecializationMaychangeovertimeMorecomplicated!.GeneexpressionineukaryoticcellTranscriptioniscommoncontrolpointRNAprocessingStabilityofRNAProteinmodification.RegulationofchromatinstructureAccesstopromotersenhancedbyhistoneacetylationHistonemethylationandphosphorylationpatternsMethylationofDNAaffectsgeneexpression(alongwithhistonedeacetylation)Canbereversed.TranscriptionofeukaryoticgenesManycontrolelements.Whatarethecomponentsoftranscriptionalregulation?TranscriptionfactorsProximalactivatorsDistalcontrolelements(enhancers)DNAbindingdomainActivationdomainsbindtootherproteinsThesearecell-specificAfewcommonstructures,butfoundindifferentcombinationsindifferentcells.Whyisthesamegeneexpressedinsomecellsbutnotothers?.Whatistheeukaryoticcounterparttoanoperon?Co-expressedgenesareusuallynotnexttoeachotherHormone-receptorcomplexcanbindtocontrolelementscommontomaygenes.SignaltransductionpathwayscanactivatemanygenesHowmanytranscriptionfactorsareactivated?CanthecomplexbindtomorethanonesiteonDNA?.“Nucleararchitecture”Arechromosomesactuallyarrangedinthenucleus?.Post-transcriptionalregulationHowmuchproteinismade?Cantheproteinbealtered?Canthetranscriptbemodifiedinresponsetochangesintheenvironment?.Post-transcriptionalregulationAlternativePNAsplicing“selection”ofexonsOnegenecangeneratemanyformsofaproteinmRNAdegradationSomemRNAsaremorestable(socanbetranslatedmoreoften)3’-UTRseemstobeimportant.Translationandbeyond5’-capand3’-poly-AtailrequiredforribosomebindingPoly-AtailcanbemodifiedtoallowbindingRegulatoryproteinscanbindtoUTRs.Post-translationalmodificationManyproteinsrequiremodificationCleavageModificationbyphosphategroups,sugars,etc.SignalpeptidesSomeproteinsaresupposedtobeshort-livedProteindegradationishighlycontrolled.mRNA,rRNA,tRNA…there’smore!NotallDNAcodesforproteinrRNA,tRNA(largenc(non-coding)RNAs)SmallRNAsareregulatorymicroRNAscanbindtocomplementarysequencesinRNAWhatwouldadouble-strandedRNAmoleculedo?.MechanismforRNAinterference(RNAi)miRNAsiRNAsdothesamethingbutareformeddifferentlyThesecanaffectchromatinpacking.EmbryonicdevelopmentandregulatedgeneexpressionOnecellgivesrisetomanyThecellsarenotthesameDifferentiateintoorgansandtissuesMorphogenesis-changeinformHow,when,andwhere?.DifferentcellsactivatedifferentgenesProcessissequentialCelldifferentiationisapathwayEndproduct:aspecializedcell.Theinformationisintheegg.Thesequentialprocessofcelldifferentiation(intherightenvironment).Howdothecellsdevelopintherightplace?Manygenesrequiredforbodyplanformation.Cancer:whencellcyclecontrolgoeswrongProto-oncogenes:theacceleratorTumorsuppressorgenes:thebrakesDNArepairAnchoringofcellsRegulatorypathways.Pathways,andsomeimportantregulatorygenes.Cancerdoesnothappeneasily.…butriskfactorscanincreaseyourchancesofcancerInheritedmutations(one“hit”hasalreadyhappened)APCp53BRCA1ExposuretoDNA-damagingsubstancesCertaintypesofviruses.SummaryBacteriacanregulatetranscriptionthroughoperonsEukaryotic