Gene Isoform Specificity through Enhancer-Associated Antisense Transcription 英文参考文献.docVIP

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Gene Isoform Specificity through Enhancer-Associated Antisense Transcription 英文参考文献.doc

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Gene Isoform Specificity through Enhancer-Associated Antisense Transcription 英文参考文献

GeneIsoformSpecificitythroughEnhancer-Associated AntisenseTranscription CourtneyS.Onodera1¤a,JasonG.Underwood1,2,3¤b,SolKatzman1,2,FrankJacobs1,2,DavidGreenberg1,4 , SofieR.Salama1,2,3*,DavidHaussler1,2,3 1DepartmentofBiomolecularEngineering,UniversityofCaliforniaSantaCruz,SantaCruz,California,UnitedStatesofAmerica,2CenterforBiomolecularSciencesand Engineering,UniversityofCaliforniaSantaCruz,SantaCruz,California,UnitedStatesofAmerica,3HowardHughesMedicalInstitute,UniversityofCaliforniaSantaCruz, SantaCruz,California,UnitedStatesofAmerica,4DepartmentofMolecular,CellandDevelopmentalBiology,UniversityofCaliforniaSantaCruz,SantaCruz,California, UnitedStatesofAmerica Abstract Enhancers and antisense RNAs play key roles in transcriptional regulation through differing mechanisms. Recent studies havedemonstratedthatenhancersareoftenassociatedwithnon-codingRNAs(ncRNAs),yetthefunctionalroleofthese enhancer:ncRNAassociationsisunclear.UsingRNA-Sequencingtointerrogatethetranscriptomesofundifferentiatedmouse embryonicstemcells(mESCs)andtheirderivedneuralprecursorcells(NPs),weidentifiedtwonovelenhancer-associated antisensetranscriptsthatappeartocontrolisoform-specificexpressionoftheiroverlappingprotein-codinggenes.Ineach case,anenhancerinternaltoaprotein-codinggenedrivesanantisenseRNAinmESCsbutnotinNPs.Expressionofthe antisenseRNAiscorrelatedwithexpressionofashorterisoformoftheassociatedsensegenethatisnotpresentwhenthe antisenseRNAisnotexpressed.Wedemonstratethatexpressionoftheantisensetranscriptsaswellasexpressionofthe short sense isoforms correlates with enhancer activity at these two loci. Further, overexpression and knockdown experiments suggest the antisense transcripts regulate expression of their associated sense genes via cis-acting mechanisms. Interestingly, the protein-coding genes involved in these two examples, Zmynd8 and Brd1, share many functional domains, yet their antisense ncRNAs show no homology to each other and are not present in non-murine mammalian lineage