ORIGINALARTICLEnpgCellResearch(2014):1-19.©2014IBCB,SIBS,CASAllrightsreserved1001-0602/14$32.00www.nature.com/crPlanthomeodomainfingerprotein2promotesboneformationbydemethylatingandactivatingRunx2forosteoblastdifferentiationHye-JinKim1,Jong-WanPark1,2,3,Kyoung-HwaLee1,2,HaejinYoon1,DongHoonShin1,2,Uk-IlJu1,SeungHyeokSeok4,SeungHyeonLim5,ZangHeeLee6,Hong-HeeKim6,Yang-SookChun1,21DepartmentofBiomedicalSciences,SeoulNationalUniversityCollegeofMedicine,Seoul110-799,RepublicofKorea;2Ischemic/HypoxicDiseaseInstitute,SeoulNationalUniversityCollegeofMedicine,Seoul110-799,RepublicofKorea;3CancerResearchInstitute,SeoulNationalUniversityCollegeofMedicine,Seoul110-799,RepublicofKorea;4DepartmentofMicrobiologyandIm-munology,SeoulNationalUniversityCollegeofMedicine,Seoul110-799,RepublicofKorea;5InstituteforExperimentalAnimals,SeoulNationalUniversityCollegeofMedicine,Seoul110-799,RepublicofKorea;6DepartmentofCellandDevelopmentalBiolo-gy,SeoulNationalUniversitySchoolofDentistry,Seoul110-749,RepublicofKoreaPlanthomeodomainfingerprotein2(PHF2),whichcontainsaplanthomeodomainandaJumonji-Cdomain,isanepigeneticregulatorthatdemethylateslysine9inhistone3(H3K9me2).Ontheotherhand,runt-relatedtran-scriptionfactor2(Runx2)playsessentialrolesinbonedevelopmentandregeneration.GivenpreviousreportsthatthePHF2mutationcancausedwarfisminmiceandthatPHF2expressioniscorrelatedwiththatofRunx2indiffer-entiatingthymocytes,weinvestigatedwhetherPHF2regulatesRunx2-mediatedboneformation.OverexpressionofPHF2facilitatedbonedevelopmentinnewbornmice,andviralshRNA-mediatedknockdownofPHF2delayedcal-varialboneregenerationinadultrats.InprimaryosteoblastsandC2C12precursorcells,PHF2enhancesosteoblastdifferentiationbydemethylatingRunx2,whilesuppressorofvariegation3-9homolog1(SUV39H1)inhibitsbonefor-mationbymethylatingit.ThePHF2-Runx2interactionismediatedbytheJumonji-CandRuntdomainsofthetwoproteins,respectively.TheinteractionbetweenRunx2andosteocalcinpromoterisregulatedbythemethylationsta-tusofRunx2,i.e.,theinteractioni...
