10034–10051NucleicAcidsResearch,2018,Vol.46,No.19Publishedonline31July2018doi:10.1093/nar/gky682ZBTB24isatranscriptionalregulatorthatcoordinateswithDNMT3BtocontrolDNAmethylationJoyceJ.Thompson1,RupinderKaur1,CarlosP.Sosa2,Jeong-HeonLee3,4,KatsunobuKashiwagi5,DanZhou6andKeithD.Robertson1,4,*1DepartmentofMolecularPharmacologyandExperimentalTherapeutics,MayoClinic,200FirstStreetSW,Stabile12-58,Rochester,MN55905,USA,2ClinicalGenomeSequencingLaboratory,DepartmentofLaboratoryMedicineandPathology,MayoClinic,200FirstStreetSW,Stabile12-58,Rochester,MN55905,USA,3DepartmentofBiochemistryandMolecularBiology,MayoClinic,Rochester,MN55905,USA,4EpigenomicsTranslationalProgram,MayoClinic,Rochester,MN55905,USA,5DepartmentofPhysiologyII,NaraMedicalUniversity,Kashihara,Nara634-8521,Japanand6InstitutesofBiomedicalSciences,ShanghaiMedicalCollege,FudanUniversity,Shanghai,ChinaReceivedMarch28,2018;RevisedJune29,2018;EditorialDecisionJuly17,2018;AcceptedJuly17,2018ABSTRACTTheinterplaybetweentranscriptionfactorsandepi-geneticwritersliketheDNAmethyltransferases(DN-MTs),andtheroleofthisinterplayingeneex-pression,isbeingincreasinglyappreciated.ZBTB24,apoorlycharacterizedzinc-fingerprotein,orthedenovomethyltransferaseDNMT3B,whenmutated,causeImmunodeficiency,CentromereInstability,andFacialanomalies(ICF)syndrome,suggestinganun-derlyingmechanisticlink.Chromatinimmunopre-cipitationcoupledwithloss-of-functionapproachesinmodelsystemsrevealedcommonlociboundbyZBTB24andDNMT3B,wheretheyfunctiontoregu-lategenebodymethylation.Genescoordinatelyreg-ulatedbyZBTB24andDNMT3Bareenrichedformolecularmechanismsessentialforcellularhome-ostasis,highlightingtheimportanceoftheZBTB24-DNMT3Binterplayinmaintainingepigeneticpatternsrequiredfornormalcellularfunction.WeidentifyaZBTB24DNAbindingmotif,whichiscontainedwithinthepromotersofmostofitstranscriptionaltargets,includingCDCA7,AXIN2,andOSTC.DirectbindingofZBTB24atthepromotersofthesegenestargetsthemfortranscriptionalactivation.ZBTB24bindingatthepromotersofRNF169andCAMK...
