The relationship between genome structure and function

Over the past 50 years it has emerged that, broadly speaking, there are three fundamental genomic DNA elements controlling gene expression: ... Skiptomaincontent Thankyouforvisitingnature.com.YouareusingabrowserversionwithlimitedsupportforCSS.Toobtain thebestexperience,werecommendyouuseamoreuptodatebrowser(orturnoffcompatibilitymodein InternetExplorer).Inthemeantime,toensurecontinuedsupport,wearedisplayingthesitewithoutstyles andJavaScript. Advertisement nature naturereviewsgenetics reviewarticles article Subjects GeneexpressionGeneregulationNuclearorganizationTranscriptionalregulatoryelements APublisherCorrectiontothisarticlewaspublishedon14October2021 Thisarticlehasbeenupdated AbstractPrecisepatternsofgeneexpressioninmetazoansarecontrolledbythreeclassesofregulatoryelements:promoters,enhancersandboundaryelements.Duringdifferentiationanddevelopment,theseelementsformspecificinteractionsindynamichigher-orderchromatinstructures.However,therelationshipbetweengenomestructureanditsfunctioningeneregulationisnotcompletelyunderstood.Herewereviewrecentprogressinthisfieldanddiscusswhethergenomestructureplaysaninstructiveroleinregulatinggeneexpressionorisareflectionoftheactivityoftheregulatoryelementsofthegenome. Thisisapreviewofsubscriptioncontent Accessoptions Accessthroughyourinstitution Changeinstitution Buyorsubscribe SubscribetoJournalGetfulljournalaccessfor1year55,14€only4,60€perissueSubscribeAllpricesareNETprices.VATwillbeaddedlaterinthecheckout.Taxcalculationwillbefinalisedduringcheckout.RentorBuyarticleGettimelimitedorfullarticleaccessonReadCube.from$8.99RentorBuyAllpricesareNETprices. Additionalaccessoptions: Login Learnaboutinstitutionalsubscriptions Fig.1:Theregulatoryelementsofthegenome.Fig.2:Theorganizationofthegenome.Fig.3:Compartmentalizationandloopextrusion.Fig.4:Therelationshipbetweenthelinearorderoftheregulatoryelementsandtheorganizationofthegenome.Fig.5:Formationofenhancer–promoterinteractionsbyloopextrusionandaffinity. 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AdditionalinformationPeerreviewinformationNatureReviewsGeneticsthanksA.Papantonis,J.Wysockaandtheother,anonymous,reviewer(s)fortheircontributiontothepeerreviewofthiswork.Publisher’snoteSpringerNatureremainsneutralwithregardtojurisdictionalclaimsinpublishedmapsandinstitutionalaffiliations.GlossaryEpigenetic Pertainstochangesinchromatinthatregister,signalorperpetuatealteredactivitystateswithoutchangingtheprimaryDNAsequence. Chromatin ThecomplexofDNAandproteinsthatmakesupchromosomes;chromatinconsistsofnucleosomesformedof~150 bpofDNAwrappedaroundahistoneoctamer,whichcanbefurtherpackagedintohigher-orderstructures. Euchromatin Arelativelylooselypackagedformofchromatinthatisenrichedingenesthatareactivelytranscribedorpoisedfortranscription. Facultativeheterochromatin Regionsofchromatinthataredenselypackagedandtranscriptionallysilentbutmaylosetheircondensedstateandbecometranscriptionallyactive. Constitutiveheterochromatin Regionsofpermanentlydenselypackagedandtranscriptionallysilentchromatinthatarefoundatspecific,highlyrepetitiveregionsofthegenome,suchastelomeresandcentromeres. Pre-initiationcomplex Alargecomplexofproteins,includingRNApolymeraseIIanditsassociatedgeneraltranscriptionfactors,whichisnecessaryforthetranscriptionofprotein-codinggenes. TATAbox NamedafteritsconservedDNAsequence,theTATAboxisanon-codingDNAsequencefoundinmanyeukaryoticcorepromotersthatrecruitsthepre-initiationcomplextoinitiatetranscription. CpGislands Regionsofthegenome(~300–3,000 bp)thatcontainalargenumberofCpGdinucleotidesandareassociatedwith~40–70%ofmammaliangenepromoters. Mediatorcomplex Alargeproteincomplexthatactsasakeytranscriptionalco-activatorbycommunicatingsignalsfromtranscriptionfactorstoRNApolymeraseIItocontrolitsactivity. Nuclearspeckles Non-membrane-boundsubdomainslocatedintheinterchromatinregionsofthenucleusofmammaliancellsthatareenrichedinsplicingfactorsandothermRNA-processingproteins. Phaseseparation Theprocessbywhichsubstancesinamixturebecomeseparatedintwodistinctphases,asoccursinamixtureofoilandwater. Polycomb ThePolycombsysteminvolvesvariousproteincomplexes,includingPolycombrepressivecomplex1(PRC1)andPRC2,whichactastranscriptionalrepressorswithakeyroleinepigeneticsilencingduringdifferentiationanddevelopment. Polycombbodies FociofPolycombgroupproteinsinthenucleusthatareinvolvedinbothgenomeorganizationandrepressionofgeneexpression. Molecularcondensates Non-membrane-boundsubcompartmentsinthenucleoplasmorcytoplasmthatarestronglyenrichedinordepletedofspecificproteinsornucleicacids. RightsandpermissionsReprintsandPermissionsAboutthisarticleCitethisarticleOudelaar,A.M.,Higgs,D.R.Therelationshipbetweengenomestructureandfunction. NatRevGenet22,154–168(2021).https://doi.org/10.1038/s41576-020-00303-xDownloadcitationAccepted:21October2020Published:24November2020IssueDate:March2021DOI:https://doi.org/10.1038/s41576-020-00303-xSharethisarticleAnyoneyousharethefollowinglinkwithwillbeabletoreadthiscontent:GetshareablelinkSorry,ashareablelinkisnotcurrentlyavailableforthisarticle.Copytoclipboard ProvidedbytheSpringerNatureSharedItcontent-sharinginitiative Accessthroughyourinstitution Changeinstitution Buyorsubscribe Advertisement Explorecontent Researcharticles Reviews&Analysis News&Comment Videos Currentissue Collections FollowusonFacebook FollowusonTwitter Subscribe Signupforalerts RSSfeed Aboutthejournal Aims&Scope JournalInformation AbouttheEditors JournalCredits Posters JournalImpact Conferences Editorialinputandchecks EditorialValuesStatement Calendars WebFeeds Contact Editorialpolicies Publishwithus ForAuthors ForReferees Submitmanuscript Search Searcharticlesbysubject,keywordorauthor Showresultsfrom Alljournals Thisjournal Search Advancedsearch Quicklinks Explorearticlesbysubject Findajob Guidetoauthors Editorialpolicies