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1、LETTERdoi:10.1038/nature20149LocalregulationofgeneexpressionbylncRNApromoters,transcriptionandsplicingJesseM.Engreitz1,2,JennaE.Haines1?,ElizabethM.Perez1,GlenMunson1,JennyChen1,2,MichaelKane1,PatrickE.McDonel1?,MitchellGuttman3&EricS.Lander1,4,5Mammaliangen
2、omesarepervasivelytranscribed1,2toproduceAt5ofthese12lncRNAloci,promoterknockoutssignificantlythousandsoflongnon-codingRNAs(lncRNAs)3,4.Afewoftheseaffectedtheexpressionofanearbygeneinanallele-specificmannerlncRNAshavebeenshowntorecruitregulatorycomplexesthro
3、ugh(falsediscoveryrate<10%),includingbothactivatingandrepressiveRNA–proteininteractionstoinfluencetheexpressionofnearbyeffects(Fig.1c,d,SupplementaryNote4andExtendedDataFig.3).genes5–7,andithasbeensuggestedthatmanyotherlncRNAscanForeachlocus,theaffectedgenew
4、aslocatedimmediatelyadjacentto,alsoactaslocalregulators8,9.Suchlocalfunctionscouldexplainandwithin5–71kbof,theknocked-outpromoter(Fig.1candExtendedtheobservationthatlncRNAexpressionisoftencorrelatedwithDataFig.4).ThisindicatesthatasubstantialfractionoflncRNA
5、locitheexpressionofnearbygenes2,10,11.However,thesecorrelationsinfluencetheexpressionofaneighbouringgene.havebeenchallengingtodissect12andcouldalternativelyresultTotestwhethersucheffectswerespecifictolncRNAloci,wefromprocessesthatarenotmediatedbythelncRNAtra
6、nscriptsdeletedthepromotersofsixprotein-codinggenes(ExtendedDatathemselves.Forexample,somegenepromotershavebeenproposedFig.1).Surprisingly,knockoutsatfouroftheselocialsoaffectedthetohavedualfunctionsasenhancers13–16,andtheprocessofexpressionofaneighbourincis
7、(Fig.1c,dandExtendedDataFig.5).transcriptionitselfmaycontributetogeneregulationbyrecruitingThus,bothnon-codingandcodinglocicandirectlyinfluencelocalactivatingfactorsorremodellingnucleosomes10,17,18.Hereweusegeneexpression.Theseregulatoryconnectionsmaycontrib
8、utetothegeneticmanipulationinmousecelllinestodissect12genomiclociobservedcorrelationsintheexpressionofneighbouringgenes,whichthatproducelncRNAsandfindthat5oftheselociinfluencethehavebeenreported
