Gene Expression and Regulation | Learn Science at Scitable

Some genes are constitutive, or always "on," regardless of environmental conditions. Such genes are among the most important elements of a cell's genome, and ... Thispagehasbeenarchivedandisnolongerupdated   GeneExpressionandRegulation Editor(s):  LauraHoopes |  Subscribe Howdoesagene,whichconsistsofastringofDNAhiddeninacell'snucleus,knowwhenitshouldexpressitself?Howdoesthisgenecausetheproductionofastringofaminoacidscalledaprotein?Howdodifferenttypesofcellsknowwhichtypesofproteinstheymustmanufacture?Theanswerstosuchquestionslieinthestudyofgeneexpression.Thus,thiscollectionorarticlesbeginsbyshowinghowaquiet,well-guardedstringofDNAisexpressedtomakeRNA,andhowthemessengerRNAistranslatedfromnucleicacidcodingtoproteincodingtoformaprotein.Alongtheway,thearticlesetalsoexaminesthenatureofthegeneticcode,howtheelementsofcodewerepredicted,andhowtheactualcodonsweredetermined.Next,weturntotheregulationofgenes.Genescan'tcontrolanorganismontheirown;rather,theymustinteractwithandrespondtotheorganism'senvironment.Somegenesareconstitutive,oralways"on,"regardlessofenvironmentalconditions.Suchgenesareamongthemostimportantelementsofacell'sgenome,andtheycontroltheabilityofDNAtoreplicate,expressitself,andrepairitself.Thesegenesalsocontrolproteinsynthesisandmuchofanorganism'scentralmetabolism.Incontrast,regulatedgenesareneededonlyoccasionally—buthowdothesegenesgetturned"on"and"off"?Whatspecificmoleculescontrolwhentheyareexpressed?Itturnsoutthattheregulationofsuchgenesdiffersbetweenprokaryotesandeukaryotes.Forprokaryotes,mostregulatoryproteinsarenegativeandthereforeturngenesoff.Here,thecellsrelyonprotein–smallmoleculebinding,inwhichaligandorsmallmoleculesignalsthestateofthecellandwhethergeneexpressionisneeded.Therepressororactivatorproteinbindsnearitsregulatorytarget:thegene.Someregulatoryproteinsmusthavealigandattachedtothemtobeabletobind,whereasothersareunabletobindwhenattachedtoaligand.Inprokaryotes,mostregulatoryproteinsarespecifictoonegene,althoughthereareafewproteinsthatactmorewidely.Forinstance,somerepressorsbindnearthestartofmRNAproductionforanentireoperon,orclusterofcoregulatedgenes.Furthermore,somerepressorshaveafine-tuningsystemknownasattenuation,whichusesmRNAstructuretostopbothtranscriptionandtranslationdependingontheconcentrationofanoperon'send-productenzymes.(Ineukaryotes,thereisnoexactequivalentofattenuation,becausetranscriptionoccursinthenucleusandtranslationoccursinthecytoplasm,makingthissortofcoordinatedeffectimpossible.)YetanotherlayerofprokaryoticregulationaffectsthestructureofRNApolymerase,whichturnsonlargegroupsofgenes.Here,thesigmafactorofRNApolymerasechangesseveraltimestoproduceheat-anddesiccation-resistantspores.Here,thearticlesonprokaryoticregulationdelveintoeachofthesetopics,leadingtoprimaryliteratureinmanycases.Foreukaryotes,cell-celldifferencesaredeterminedbyexpressionofdifferentsetsofgenes.Forinstance,anundifferentiatedfertilizedegglooksandactsquitedifferentfromaskincell,aneuron,oramusclecellbecauseofdifferencesinthegeneseachcellexpresses.Acancercellactsdifferentfromanormalcellforthesamereason:Itexpressesdifferentgenes.(Usingmicroarrayanalysis,scientistscanusesuchdifferencestoassistindiagnosisandselectionofappropriatecancertreatment.)Interestingly,ineukaryotes,thedefaultstateofgeneexpressionis"off"ratherthan"on,"asinprokaryotes.Whyisthisthecase?Thesecretliesinchromatin,orthecomplexofDNAandhistoneproteinsfoundwithinthecellularnucleus.Thehistonesareamongthemostevolutionarilyconservedproteinsknown;theyarevitalforthewell-beingofeukaryotesandbrooklittlechange.Whenaspecificgeneistightlyboundwithhistone,thatgeneis"off."Buthow,then,doeukaryoticgenesmanagetoescapethissilencing?Thisiswherethehistonecodecomesintoplay.Thiscodeincludesmodificationsofthehistones'positivelychargedaminoacidstocreatesomedomainsinwhichDNAismoreopenandothersinwhichitisverytightlyboundup.DNAmethylationisonemechanismthatappearstobecoordinatedwithhistonemodifications,particularlythosethatleadtosilencingofgeneexpression.SmallnoncodingRNAssuchasRNAicanalsobeinvolvedintheregulatoryprocessesthatform"silent"chromatin.Ontheotherhand,whenthetailsofhistonemoleculesareacetylatedatspecificlocations,thesemoleculeshavelessinteractionwithDNA,therebyleavingitmoreopen.Theregulationoftheopeningofsuchdomainsisahottopicinresearch.Forinstance,researchersnowknowthatcomplexesofproteinscalledchromatinremodelingcomplexesuseATPtorepackageDNAinmoreopenconfigurations.ScientistshavealsodeterminedthatitispossibleforcellstomaintainthesamehistonecodeandDNAmethylationpatternsthroughmanycelldivisions.Thispersistencewithoutrelianceonbasepairingiscalledepigenetics,andthereisabundantevidencethatepigeneticchangescausemanyhumandiseases.Fortranscriptiontooccur,theareaaroundaprospectivetranscriptionzoneneedstobeunwound.Thisisacomplexprocessrequiringthecoordinationofhistonemodifications,transcriptionfactorbindingandotherchromatinremodelingactivities.OncetheDNAisopen,specificDNAsequencesarethenaccessibleforspecificproteinstobind.Manyoftheseproteinsareactivators,whileothersarerepressors;ineukaryotes,allsuchproteinsareoftencalledtranscriptionfactors(TFs).EachTFhasaspecificDNAbindingdomainthatrecognizesa6-10base-pairmotifintheDNA,aswellasaneffectordomain.Inthetesttube,scientistscanfindafootprintofaTFifthatproteinbindstoitsmatchingmotifinapieceofDNA.TheycanalsoseewhetherTFbindingslowsthemigrationofDNAingelelectrophoresis.ForanactivatingTF,theeffectordomainrecruitsRNApolymeraseII,theeukaryoticmRNA-producingpolymerase,tobegintranscriptionofthecorrespondinggene.SomeactivatingTFseventurnonmultiplegenesatonce.AllTFsbindatthepromotersjustupstreamofeukaryoticgenes,similartobacterialregulatoryproteins.However,theyalsobindatregionscalledenhancers,whichcanbeorientedforwardorbackwardsandlocatedupstreamordownstreamorevenintheintronsofagene,andstillactivategeneexpression.Becausemanygenesarecoregulated,studyinggeneexpressionacrossthewholegenomeviamicroarraysormassivelyparallelsequencingallowsinvestigatorstoseewhichgroupsofgenesarecoregulatedduringdifferentiation,cancer,andotherstatesandprocesses.MosteukaryotesalsomakeuseofsmallnoncodingRNAstoregulategeneexpression.Forexample,theenzymeDicerfindsdouble-strandedregionsofRNAandcutsoutshortpiecesthatcanserveinaregulatoryrole.ArgonauteisanotherenzymethatisimportantinregulationofsmallnoncodingRNA–dependentsystems.HereweoffferanintroductoryarticleontheseRNAs,butmorecontentisneeded;pleasecontacttheeditorsifyouareinterestedincontributing.Imprintingisyetanotherprocessinvolvedineukaryoticgeneregulation;thisprocessinvolvesthesilencingofoneofthetwoallelesofageneforacell'sentirelifespan.Imprintingaffectsaminorityofgenes,butseveralimportantgrowthregulatorsareincluded.Forsomegenes,thematernalcopyisalwayssilenced,whilefordifferentgenes,thepaternalcopyisalwayssilenced.Theepigeneticmarksplacedonthesegenesduringeggorspermformationarefaithfullycopiedintoeachsubsequentcell,therebyaffectingthesegenesthroughoutthelifeoftheorganism.Stillanothermechanismthatcausessomegenestobesilencedforanorganism'sentirelifetimeisXinactivation.Infemalemammals,forinstance,oneofthetwocopiesoftheXchromosomeisshutoffandcompactedgreatly.Thisshutoffprocessrequirestranscription,theparticipationoftwononcodingRNAs(oneofwhichcoatstheinactiveXchromosome),andtheparticipationofaDNA-bindingproteincalledCTCF.AsthepossibleroleofregulatorynoncodingRNAsinthisprocessisinvestigated,moreinformationregardingXinactivationwillnodoubtbediscovered.Image:'Illumination'byPatrickMorgan,fromthecoverofNatureReviewsGenetics,June2006.Allrightsreserved.Hoopes,L.(2008)Introductiontothegeneexpressionandregulationtopicroom.NatureEducation1(1):160 More Close share Close Digg MySpace Google+ RelatedContent Blogs&Forums Spotlights   RelatedSubjects Select GeneInheritanceandTransmission NucleicAcidStructureandFunction ChromosomesandCytogenetics EvolutionaryGenetics PopulationandQuantitativeGenetics Genomics GenesandDisease GeneticsandSociety   MoreTopicRooms Select Genetics CellBiology ScientificCommunication CareerPlanning   ExploreThisSubject ConsequencesofGeneRegulation Atavism:Embryology,DevelopmentandEvolution Epistasis:GeneInteractionandthePhenotypicExpressionofComplexDiseasesLikeAlzheimer's GeneInteractionandDisease GeneticControlofAgingandLifeSpan GeneticDiagnosis:DNAMicroarraysandCancer GeneticImprintingandXInactivation GeneticRegulationofCancer ImprintingandGeneticDisease:Angelman,Prader-WilliandBeckwith-WeidemannSyndromes Obesity,Epigenetics,andGeneRegulation OrganizationofChromatin ChromatinRemodelingandDNase1Sensitivity ChromatinRemodelinginEukaryotes ExaminingHistoneModificationswithChromatinImmunoprecipitationandQuantitativePCR TheComplexityofGeneExpression,ProteinInteraction,andCellDifferentiation TheRoleofMethylationinGeneExpression TranscriptionFactors HoxGenesinDevelopment:TheHoxCode DoTranscriptionFactorsActuallyBindDNA?DNAFootprintingandGelShiftAssays GeneExpressionRegulatesCellDifferentiation GeneticSignaling:TranscriptionFactorCascadesandSegmentation Gradient-BasedDNATranscriptionControlinAnimals TheComplexityofGeneExpression,ProteinInteraction,andCellDifferentiation TranscriptionFactorsandTranscriptionalControlinEukaryoticCells FromDNAtoProtein DiscoveringtheRelationshipBetweenDNAandProteinProduction DNATranscription NucleicAcidstoAminoAcids:DNASpecifiesProtein ReadingtheGeneticCode SimultaneousGeneTranscriptionandTranslationinBacteria Translation:DNAtomRNAtoProtein RegulationofTranscription GeneExpressionRegulatesCellDifferentiation NegativeTranscriptionRegulationinProkaryotes OperonsandProkaryoticGeneRegulation PositiveTranscriptionControl:TheGlucoseEffect RegulationofTranscriptionandGeneExpressioninEukaryotes TheRoleofMethylationinGeneExpression TranscriptionFactorsandTranscriptionalControlinEukaryoticCells GeneResponsestoEnvironment EnvironmentControlsGeneExpression:SexDeterminationandtheOnsetofGeneticDisorders EnvironmentalCuesLikeHypoxiaCanTriggerGeneExpressionandCancerDevelopment EnvironmentalFactorsLikeViralInfectionsPlayaRoleintheOnsetofComplexDiseases EnvironmentalInfluencesonGeneExpression EnvironmentalMutagens,CellSignallingandDNARepair GeneExpressionRegulatesCellDifferentiation Genes,Smoking,andLungCancer Obesity,Epigenetics,andGeneRegulation TheComplexityofGeneExpression,ProteinInteraction,andCellDifferentiation RNA mRNA:HistoryofFunctionalInvestigation RNAFunctions RNATranscriptionbyRNAPolymerase:ProkaryotesvsEukaryotes SmallNon-codingRNAandGeneExpression ScitableChat Register | SignIn   Library   GeneticsTopicRoom   GeneExpressionandRegulation