Associateeditor:B.TeicherEpigenetictargetsanddrugdiscoveryPart1:HistonemethylationYanliLiua,b,1,KeLiua,b,1,SuQinb,ChaoXub,JinrongMina,b,c,⁎aHubeiKeyLaboratoryofGeneticRegulationandIntegrativeBiology,CollegeofLifeScience,CentralChinaNormalUniversity,Wuhan430079,PRChinabStructuralGenomicsConsortium,UniversityofToronto,101CollegeStreet,Toronto,OntarioM5G1L7,CanadacDepartmentofPhysiology,UniversityofToronto,Toronto,OntarioM5S1A8,CanadaabstractarticleinfoKeywords:EpigeneticsHistonemethylationInhibitorChemicalprobeCancerDynamicchromatinstructureismodulatedbypost-translationalmodificationsonhistones,suchasacetylation,phosphorylationandmethylation.Researchonhistonemethylationhasbecomethemostflourishingareaofepi-geneticsinthepastfourteenyears,andalargeamountofdatahasbeenaccumulatedregardingitsbiologyanddiseaseimplications.Correspondingly,alotofeffortshavebeenmadetodevelopsmallmoleculecompoundsthatcanspecificallymodulatehistonemethyltransferasesandmethylationreaderproteins,aimingforpotentialtherapeuticdrugs.Here,wesummarizerecentprogressinchemicalprobeanddrugdiscoveryofhistonemeth-yltransferasesandmethylationreaderproteins.Foreachtarget,wewillreviewtheirbiological/biochemicalfunc-tionsfirst,andthenfocusontheirdiseaseimplicationsanddrugdiscovery.Wecanalsoseethatstructure-basedcompounddesignandoptimizationplaysacriticalroleinfacilitatingthedevelopmentofhighlypotentandselectivechemicalprobesandinhibitorsforthesetargets.©2014ElsevierInc.Allrightsreserved.Contents1.Introduction................................................02.G9a/GLP:apairofcloselyhomologoushistoneH3K9me1/2methyltransferases.................03.Suv39H1/2:apairofcloselyhomologoushistoneH3K9me3methyltransferases.................04.DOT1L:ahistoneH3K79methyltransferase..................................05.EZH2andthePRC2complex:ahistoneH3K27methyltransferase........................06.Otherhistone/proteinmethyltransferasesandinhibitors............................07.MBTrepeatdomainproteins:mono-anddi-methyllysinebind...
