TranscriptionfactorsasreadersandeffectorsofDNAmethylationHengZhu1,2,GuohuaWang3,andJiangQian2,31DepartmentofPharmacologyandMolecularSciences,JohnsHopkinsSchoolofMedicine,EdwardMillerResearchBuilding,733NorthBroadway,Baltimore,Maryland21205,USA2TheSidneyKimmelComprehensiveCancerCenter,JohnsHopkinsSchoolofMedicine,Baltimore,Maryland21287,USA3TheWilmerEyeInstitute,JohnsHopkinsSchoolofMedicine,TheSmithBuilding,400NorthBroadway,Baltimore,Maryland21287,USAAbstractRecenttechnologicaladvanceshavemadeitpossibletodecodeDNAmethylomesatsingle-base-pairresolutionundervariousphysiologicalconditions.Manyaberrantordifferentiallymethylatedsiteshavebeendiscovered,butthemechanismsbywhichchangesinDNAmethylationleadtoobservedphenotypes,suchascancer,remainelusive.Theclassicalviewofmethylation-mediatedprotein-DNAinteractionsisthatonlyproteinswithamethyl-CpGbindingdomain(MBD)caninteractwithmethylatedDNA.However,evidenceisemergingtosuggestthattranscriptionfactorslackingaMBDcanalsointeractwithmethylatedDNA.Theidentificationoftheseproteinsandtheelucidationoftheircharacteristicsandthebiologicalconsequencesofmethylation-dependenttranscriptionfactor-DNAinteractionsareimportantsteppingstonestowardsamechanisticunderstandingofmethylation-mediatedbiologicalprocesses,whichhavecrucialimplicationsforhumandevelopmentanddisease.DNAmethylation,oneofthebest-studiedepigeneticmarksineukaryotes,isabiologicalprocessinwhichamethylgroupiscovalentlyaddedtoacytosine,yielding5-methylcytosine(5mC)1–3(BOX1).ThemethylationprocessiscarriedoutbyasetofenzymescalledDNAmethyltransferases(DNMTs)4,whichareencodedinmanygenomes,frombacteriatoplantsandmammals5,6.TheevolutionaryconservationoftheseenzymessuggeststhatDNAmethylationprovidesaselectiveadvantagetotheorganism.However,thepercentageofCorrespondencetoH.Z.andJ.Q.hzhu4@jhmi.edu;jiang.qian@jhmi.edu.CompetinginterestsstatementTheauthorsdeclarenocompetinginterests.DATABASESENCODE:http://encodeproject.orgENCSR000EBQ|ENCSR000EBV|ENCSR000BSI|ENCSR000ECC|ENCSR000ECF|ENCSR000BJ...
