Regulation of Gene Expression | Biology for Majors I

Gene regulation is the process of controlling which genes in a cell's DNA are expressed (used to make a functional product such as a protein). · Different cells ... Skiptomaincontent BiologyforMajorsI Module11:GeneExpression Searchfor: RegulationofGeneExpression Definethetermregulationasitappliestogenes Foracelltofunctionproperly,necessaryproteinsmustbesynthesizedatthepropertime.AllcellscontrolorregulatethesynthesisofproteinsfrominformationencodedintheirDNA.TheprocessofturningonagenetoproduceRNAandproteiniscalledgeneexpression.Whetherinasimpleunicellularorganismoracomplexmulti-cellularorganism,eachcellcontrolswhenandhowitsgenesareexpressed.Forthistooccur,theremustbeamechanismtocontrolwhenageneisexpressedtomakeRNAandprotein,howmuchoftheproteinismade,andwhenitistimetostopmakingthatproteinbecauseitisnolongerneeded. Theregulationofgeneexpressionconservesenergyandspace.Itwouldrequireasignificantamountofenergyforanorganismtoexpresseverygeneatalltimes,soitismoreenergyefficienttoturnonthegenesonlywhentheyarerequired.Inaddition,onlyexpressingasubsetofgenesineachcellsavesspacebecauseDNAmustbeunwoundfromitstightlycoiledstructuretotranscribeandtranslatetheDNA.Cellswouldhavetobeenormousifeveryproteinwereexpressedineverycellallthetime. Thecontrolofgeneexpressionisextremelycomplex.Malfunctionsinthisprocessaredetrimentaltothecellandcanleadtothedevelopmentofmanydiseases,includingcancer. LearningObjectives Discusswhyeverycelldoesnotexpressallofitsgenes Compare prokaryoticandeukaryoticgeneregulation ExpressionofGenes Foracelltofunctionproperly,necessaryproteinsmustbesynthesizedatthepropertime.AllcellscontrolorregulatethesynthesisofproteinsfrominformationencodedintheirDNA.TheprocessofturningonagenetoproduceRNAandproteiniscalledgeneexpression.Whetherinasimpleunicellularorganismoracomplexmulti-cellularorganism,eachcellcontrolswhenandhowitsgenesareexpressed.Forthistooccur,theremustbeamechanismtocontrolwhenageneisexpressedtomakeRNAandprotein,howmuchoftheproteinismade,andwhenitistimetostopmakingthatproteinbecauseitisnolongerneeded. Theregulationofgeneexpressionconservesenergyandspace.Itwouldrequireasignificantamountofenergyforanorganismtoexpresseverygeneatalltimes,soitismoreenergyefficienttoturnonthegenesonlywhentheyarerequired.Inaddition,onlyexpressingasubsetofgenesineachcellsavesspacebecauseDNAmustbeunwoundfromitstightlycoiledstructuretotranscribeandtranslatetheDNA.Cellswouldhavetobeenormousifeveryproteinwereexpressedineverycellallthetime. Thecontrolofgeneexpressionisextremelycomplex.Malfunctionsinthisprocessaredetrimentaltothecellandcanleadtothedevelopmentofmanydiseases,includingcancer. Generegulationmakescellsdifferent Generegulationishowacellcontrolswhichgenes,outofthemanygenesinitsgenome,are“turnedon”(expressed).Thankstogeneregulation,eachcelltypeinyourbodyhasadifferentsetofactivegenes—despitethefactthatalmostallthecellsofyourbodycontaintheexactsameDNA.Thesedifferentpatternsofgeneexpressioncauseyourvariouscelltypestohavedifferentsetsofproteins,makingeachcelltypeuniquelyspecializedtodoitsjob. Forexample,oneofthejobsoftheliveristoremovetoxicsubstanceslikealcoholfromthebloodstream.Todothis,livercellsexpressgenesencodingsubunits(pieces)ofanenzymecalledalcoholdehydrogenase.Thisenzymebreaksalcoholdownintoanon-toxicmolecule.Theneuronsinaperson’sbraindon’tremovetoxinsfromthebody,sotheykeepthesegenesunexpressed,or“turnedoff.”Similarly,thecellsoftheliverdon’tsendsignalsusingneurotransmitters,sotheykeepneurotransmittergenesturnedoff(Figure1). Figure1.Differentcellshavedifferentgenes“turnedon.” Therearemanyothergenesthatareexpresseddifferentlybetweenlivercellsandneurons(oranytwocelltypesinamulticellularorganismlikeyourself). Howdocells“decide”whichgenestoturnon? Nowthere’satrickyquestion!Manyfactorsthatcanaffectwhichgenesacellexpresses.Differentcelltypesexpressdifferentsetsofgenes,aswesawabove.However,twodifferentcellsofthesametypemayalsohavedifferentgeneexpressionpatternsdependingontheirenvironmentandinternalstate. Broadlyspeaking,wecansaythatacell’sgeneexpressionpatternisdeterminedbyinformationfrombothinsideandoutsidethecell. Examplesofinformationfrominsidethecell:theproteinsitinheritedfromitsmothercell,whetheritsDNAisdamaged,andhowmuchATPithas. Examplesofinformationfromoutsidethecell:chemicalsignalsfromothercells,mechanicalsignalsfromtheextracellularmatrix,andnutrientlevels. Howdothesecueshelpacell“decide”whatgenestoexpress?Cellsdon’tmakedecisionsinthesensethatyouorIwould.Instead,theyhavemolecularpathwaysthatconvertinformation—suchasthebindingofachemicalsignaltoitsreceptor—intoachangeingeneexpression. Asanexample,let’sconsiderhowcellsrespondtogrowthfactors.Agrowthfactorisachemicalsignalfromaneighboringcellthatinstructsatargetcelltogrowanddivide.Wecouldsaythatthecell“notices”thegrowthfactorand“decides”todivide,buthowdotheseprocessesactuallyoccur? Figure2.Growthfactorpromptingcell division Thecelldetectsthegrowthfactorthroughphysicalbindingofthegrowthfactortoareceptorproteinonthecellsurface. Bindingofthegrowthfactorcausesthereceptortochangeshape,triggeringaseriesofchemicaleventsinthecellthatactivateproteinscalledtranscriptionfactors. ThetranscriptionfactorsbindtocertainsequencesofDNAinthenucleusandcausetranscriptionofcelldivision-relatedgenes. Theproductsofthesegenesarevarioustypesofproteinsthatmakethecelldivide(drivecellgrowthand/orpushthecellforwardinthecellcycle). Thisisjustoneexampleofhowacellcanconvertasourceofinformationintoachangeingeneexpression.Therearemanyothers,andunderstandingthelogicofgeneregulationisanareaofongoingresearchinbiologytoday. Growthfactorsignalingiscomplexandinvolvestheactivationofavarietyoftargets,includingbothtranscriptionfactorsandnon-transcriptionfactorproteins. InSummary:ExpressionofGenes Generegulationistheprocessofcontrollingwhichgenesinacell’sDNAareexpressed(usedtomakeafunctionalproductsuchasaprotein). Differentcellsinamulticellularorganismmayexpressverydifferentsetsofgenes,eventhoughtheycontainthesameDNA. ThesetofgenesexpressedinacelldeterminesthesetofproteinsandfunctionalRNAsitcontains,givingititsuniqueproperties. Ineukaryoteslikehumans,geneexpressioninvolvesmanysteps,andgeneregulationcanoccuratanyofthesesteps.However,manygenesareregulatedprimarilyattheleveloftranscription. ShowReferences Alcoholdehydrogenase.(2016,January6).RetrievedApril26,2016fromWikipedia:https://en.wikipedia.org/wiki/Alcohol_dehydrogenase. Cooper,G.M.(2000).Regulationoftranscriptionineukaryotes.InThecell:Amolecularapproach.Sunderland,MA:SinauerAssociates.Retrievedfromhttp://www.ncbi.nlm.nih.gov/books/NBK9904/. Kimball,JohnW.(2014,April19).Thehumanandchimpanzeegenomes.InKimball’sbiologypages.Retrievedfromhttp://www.biology-pages.info/H/HominoidClade.html. OpenStaxCollege,Biology.(2016,March23).Eukaryotictranscriptiongeneregulation.In_OpenStaxCNX.Retrievedfromhttp://cnx.org/contents/[email protected]:7Ry3oRse@5/Eukaryotic-Transcription-Gene-. OpenStaxCollege,Biology.(2016,March23).Regulationofgeneexpression.In_OpenStaxCNX.Retrievedfromhttp://cnx.org/contents/[email protected]:dQV50wLv@7/Regulation-of-Gene-Expression Phillips,T.(2008).Regulationoftranscriptionandgeneexpressionineukaryotes.NatureEducation,1(1),199.Retrievedfromhttp://www.nature.com/scitable/topicpage/regulation-of-transcription-and-gene-expression-in-1086. Purves,W.K.,Sadava,D.E.,Orians,G.H.,andHeller,H.C.(2003).Transcriptionalregulationofgeneexpression.InLife:Thescienceofbiology(7thed.,pp.290-296).Sunderland,MA:SinauerAssociates. Reece,J.B.,Urry,L.A.,Cain,M.L.,Wasserman,S.A.,Minorsky,P.V.,andJackson,R.B.(2011).Eukaryoticgeneexpressionisregulatedatmanystages.InCampbellBiology(10thed.,pp.365-373).SanFrancisco,CA:Pearson. ProkaryoticandEukaryoticGeneRegulation Tounderstandhowgeneexpressionisregulated,wemustfirstunderstandhowagenecodesforafunctionalproteininacell.Theprocessoccursinbothprokaryoticandeukaryoticcells,justinslightlydifferentmanners. Prokaryoticorganismsaresingle-celledorganismsthatlackacellnucleus,andtheirDNAthereforefloatsfreelyinthecellcytoplasm.Tosynthesizeaprotein,theprocessesoftranscriptionandtranslationoccuralmostsimultaneously.Whentheresultingproteinisnolongerneeded,transcriptionstops.Asaresult,theprimarymethodtocontrolwhattypeofproteinandhowmuchofeachproteinisexpressedinaprokaryoticcellistheregulationofDNAtranscription.Allofthesubsequentstepsoccurautomatically.Whenmoreproteinisrequired,moretranscriptionoccurs.Therefore,inprokaryoticcells,thecontrolofgeneexpressionismostlyatthetranscriptionallevel. Eukaryoticcells,incontrast,haveintracellularorganellesthataddtotheircomplexity.Ineukaryoticcells,theDNAiscontainedinsidethecell’snucleusandthereitistranscribedintoRNA.ThenewlysynthesizedRNAisthentransportedoutofthenucleusintothecytoplasm,whereribosomestranslatetheRNAintoprotein.Theprocessesoftranscriptionandtranslationarephysicallyseparatedbythenuclearmembrane;transcriptionoccursonlywithinthenucleus,andtranslationoccursonlyoutsidethenucleusinthecytoplasm.Theregulationofgeneexpressioncanoccuratallstagesoftheprocess(Figure1).RegulationmayoccurwhentheDNAisuncoiledandloosenedfromnucleosomestobindtranscriptionfactors(epigeneticlevel),whentheRNAistranscribed(transcriptionallevel),whentheRNAisprocessedandexportedtothecytoplasmafteritistranscribed(post-transcriptionallevel),whentheRNAistranslatedintoprotein(translationallevel),oraftertheproteinhasbeenmade(post-translationallevel). Figure1.Prokaryotictranscriptionandtranslationoccursimultaneouslyinthecytoplasm,andregulationoccursatthetranscriptionallevel.EukaryoticgeneexpressionisregulatedduringtranscriptionandRNAprocessing,whichtakeplaceinthenucleus,andduringproteintranslation,whichtakesplaceinthecytoplasm.Furtherregulationmayoccurthroughpost-translationalmodificationsofproteins. ThedifferencesintheregulationofgeneexpressionbetweenprokaryotesandeukaryotesaresummarizedinTable1.Theregulationofgeneexpressionisdiscussedindetailinsubsequentmodules. Table1. DifferencesintheRegulationofGeneExpressionofProkaryoticandEukaryoticOrganisms Prokaryoticorganisms Eukaryoticorganisms Lacknucleus Containnucleus DNAisfoundinthecytoplasm DNAisconfinedtothenuclearcompartment RNAtranscriptionandproteinformationoccuralmostsimultaneously RNAtranscriptionoccurspriortoproteinformation,andittakesplaceinthenucleus.TranslationofRNAtoproteinoccursinthecytoplasm. Geneexpressionisregulatedprimarilyatthetranscriptionallevel Geneexpressionisregulatedatmanylevels(epigenetic,transcriptional,nuclearshuttling,post-transcriptional,translational,andpost-translational) EvolutionofGeneRegulation Prokaryoticcellscanonlyregulategeneexpressionbycontrollingtheamountoftranscription.Aseukaryoticcellsevolved,thecomplexityofthecontrolofgeneexpressionincreased.Forexample,withtheevolutionofeukaryoticcellscamecompartmentalizationofimportantcellularcomponentsandcellularprocesses.AnuclearregionthatcontainstheDNAwasformed.Transcriptionandtranslationwerephysicallyseparatedintotwodifferentcellularcompartments.Itthereforebecamepossibletocontrolgeneexpressionbyregulatingtranscriptioninthenucleus,andalsobycontrollingtheRNAlevelsandproteintranslationpresentoutsidethenucleus. Somecellularprocessesarosefromtheneedoftheorganismtodefenditself.Cellularprocessessuchasgenesilencingdevelopedtoprotectthecellfromviralorparasiticinfections.Ifthecellcouldquicklyshutoffgeneexpressionforashortperiodoftime,itwouldbeabletosurviveaninfectionwhenotherorganismscouldnot.Therefore,theorganismevolvedanewprocessthathelpeditsurvive,anditwasabletopassthisnewdevelopmenttooffspring. PracticeQuestions Controlofgeneexpressionineukaryoticcellsoccursatwhichlevel(s)? onlythetranscriptionallevel epigeneticandtranscriptionallevels epigenetic,transcriptional,andtranslationallevels epigenetic,transcriptional,post-transcriptional,translational,andpost-translationallevels ShowAnswer Answerd.Controlofgeneexpressionineukaryoticcellsoccursatepigenetic,transcriptional,post-transcriptional,translational,andpost-translationallevels. Post-translationalcontrolreferstothe: regulationofgeneexpressionaftertranscription regulationofgeneexpressionaftertranslation controlofepigeneticactivation periodbetweentranscriptionandtranslation ShowAnswer Answerb. Post-translationalcontrolreferstotheregulationofgeneexpressionaftertranslation CheckYourUnderstanding Answerthequestion(s)belowtoseehowwellyouunderstandthetopicscoveredintheprevioussection.Thisshortquizdoes not counttowardyourgradeintheclass,andyoucanretakeitanunlimitednumberoftimes. Usethisquiztocheckyourunderstandinganddecidewhetherto(1)studytheprevioussectionfurtheror(2)moveontothenextsection. LicensesandAttributions CClicensedcontent,OriginalIntroductiontoRegulationofGeneExpression.Authoredby:ShelliCarterandLumenLearning.Providedby:LumenLearning.License:CCBY:AttributionCClicensedcontent,SharedpreviouslyBiology.Providedby:OpenStaxCNX.Locatedat:http://cnx.org/contents/[email protected]:CCBY:Attribution.LicenseTerms:Downloadforfreeathttp://cnx.org/contents/[email protected]:Eukaryoticgeneregulation.Providedby:KhanAcademy.Locatedat:https://www.khanacademy.org/science/biology/gene-regulation/gene-regulation-in-eukaryotes/a/overview-of-eukaryotic-gene-regulation.License:CCBY-NC-SA:Attribution-NonCommercial-ShareAlike Previous Next