1RYBPExpressionIsRegulatedbyKLF4andSp1andIsRelatedtoHepatocellularCarcinomaPrognosisQiaojiajieZhao1,4,WeihuaCai2,4,XuanZhang1,ShuoTian1,JunwenZhang1,HaiboLi3,CongcongHou1,XiaoliMa1,HongChen1,BingrenHuang1*,andDengChen1*1StateKeyLaboratoryofMedicalMolecularBiology,DepartmentofBiochemistryandMolecularBiology,InstituteofBasicMedicalSciences,ChineseAcademyofMedicalSciencesandSchoolofBasicMedicine,PekingUnionMedicalCollege,Beijing100005,China2DepartmentofHepatobiliarySurgery,NantongThirdHospital,NantongUniversity,Nantong,Jiangsu226006,China3DepartmentofClinicalLaboratoryMedicine,NantongMaternalandChildHealthHospital,Nantong,Jiangsu226018,ChinaRunningtitle:RYBPExpressionIsRegulatedbyKLF4andSp1inHCC4Theseauthorscontributedequallytothiswork.*Correspondingauthors:DengChen,Ph.D.,orBingrenHuang,Ph.D.,StateKeyLaboratoryofMedicalMolecularBiology,DepartmentofBiochemistryandMolecularBiology,InstituteofBasicMedicalSciences,ChineseAcademyofMedicalSciencesandPekingUnionMedicalCollege,5DongDanSanTiao,Beijing100005,China.Tel:86-10-69156980,E-mail:chendeng2001@hotmail.comorhbr541@hotmail.comKeywords:RYBP,KLF4,Sp1,promoter,geneexpression,generegulation,hepatocellularcarcinomahttp://www.jbc.org/cgi/doi/10.1074/jbc.M116.770727ThelatestversionisatJBCPapersinPress.PublishedonDecember27,2016asManuscriptM116.770727Copyright2016byTheAmericanSocietyforBiochemistryandMolecularBiology,Inc.byguestonDecember30,2016http://www.jbc.org/Downloadedfrom2ABSTRACTTheexpressionofRing1andYY1bindingprotein(RYBP)isreducedinseveralhumancancers,butthemolecularmechanism(s)haveremainedelusive.Inthisstudy,weusedhumanHCCcelllinesandtissuespecimenstostudythemechanism,andhereinreportseveralnewfindings.First,weclonedandcharacterizedthebasalpromoterregionofthehumanrybpgene.WefoundthatthedecreasedRYBPexpressioninHCCtissueswasnotduetopromotersequencevariation/polymorphismsorCpGdinucleotidemethylation.Weidentifiedtwotranscriptionfactors,KLF4andSp1,whichdirectlybindthepromoterregionofrybptorespectivelyinduceandsuppressryb...
