Publishedonline18October2018NucleicAcidsResearch,2018,Vol.46,No.2211759–11775doi:10.1093/nar/gky923Longnon-codingRNAChRO1facilitatesATRX/DAXX-dependentH3.3depositionfortranscription-associatedheterochromatinreorganizationJinyoungPark1,HongminLee1,NamshikHan2,SojungKwak3,Han-TeoLee4,Jae-HwanKim3,KeonjinKang1,ByoungHaYoun5,Jae-HyunYang6,Hyeon-JuJeong7,Jong-SunKang7,Seon-YoungKim5,Jeung-WhanHan1,Hong-DukYoun3,4andEun-JungCho1,*1SchoolofPharmacy,SungkyunkwanUniversity,Suwon,Gyeonggi-do16419,RepublicofKorea,2MilnerTherapeuticsInstitute,UniversityofCambridge,CambridgeCB21QN,UK,3DepartmentofBiomedicalSciences,NationalCreativeResearchCenterforEpigenomeReprogrammingNetwork,Ischemic/HypoxicDiseaseInstitute,SeoulNationalUniversityCollegeofMedicine,Seoul03080,RepublicofKorea,4DepartmentofMolecularMedicine&BiopharmaceuticalSciences,GraduateSchoolofConvergenceScienceandtechnology,SeoulNationalUniversity,Seoul03080,RepublicofKorea,5MedicalGenomeResearchCenter,KRIBB,Daejeon34141,RepublicofKorea,6DepartmentofGenetics,PaulF.GlennCenterfortheBiologyofAging,HarvardMedicalSchool,Boston,MA02115,USAand7CollegeofMedicine,SungkyunkwanUniversity,Suwon,Gyeonggi-do440-746,RepublicofKoreaReceivedApril14,2018;RevisedSeptember20,2018;EditorialDecisionSeptember21,2018;AcceptedOctober05,2018ABSTRACTConstitutiveheterochromatinundergoesadynamicclusteringandspatialreorganizationduringmyo-genicdifferentiation.Howeverthedetailedmech-anismsanditsroleincelldifferentiationremainlargelyelusive.Here,wereporttheidentificationofamuscle-specificlongnon-codingRNA,ChRO1,in-volvedinconstitutiveheterochromatinreorganiza-tion.ChRO1isinducedduringterminaldifferenti-ationofmyoblasts,andisspecificallylocalizedtothechromocentersinmyotubes.ChRO1isrequiredforefficientcelldifferentiation,withglobalimpactsongeneexpression.ItinfluencesDNAmethylationandchromatincompactionatperi/centromericre-gions.InhibitionofChRO1leadstodefectsinthespatialfusionofchromocenters,andmislocalizationofH4K20trimethylation,Suv420H2,HP1,MeCP2and...