715Livingorganismsandindividualcellsmanageenvironmentalvariationswithrapidandstablealterationsingeneexpres-sion.Thekeytothisadaptiveagencyisthechromatinpolymer,adynamicconstituentassemblyofDNAandvariousnucleo-proteinsthatspatiallyregulatestranscriptionalcompetencybystructuraladaptationandgenomecompartmentalization.Covalentepigeneticmodificationimpartingfunctionalmodu-lationandstructuralchromatinreorganizationthatpotentiateawiderangeofadaptivephenotypesareincreasinglyexaminedinhumanhealthanddisease.Theimmediatecellularenvironmentprovidesthecontextualdeterminantsofepigeneticchromatinarchitecture.Evidencefortheintegrationofsubcellular,global,andexternalmetabolicinformationintothisintricatesystemofgeneregulationhasrecentlybeguntoemerge.Chromatinmodificationasastablesystemofmetabolicin-formationcanbeobservedatregulatoryandcodingelementsofmanygenesimplicatedinmetabolism.Postreplicativemeth-ylationofDNApredominantlyatthe5-carbonringofcytosineReview©2015AmericanHeartAssociation,Inc.CirculationResearchisavailableathttp://circres.ahajournals.orgDOI:10.1161/CIRCRESAHA.116.303936Abstract:Themolecularsignaturesofepigeneticregulationandchromatinarchitecturesarefundamentaltogeneticallydeterminedbiologicalprocesses.Covalentandpost-translationalchemicalmodificationofthechromatintemplatecansensitizethegenometochangingenvironmentalconditionstoestablishdiversefunctionalstates.Recentinterestandresearchfocussurroundsthedirectconnectionsbetweenmetabolismandchromatindynamics,whichnowrepresentsanimportantconceptualchallengetoexplainmanyaspectsofmetabolicdysfunction.Severalcomponentsoftheepigeneticmachineryrequireintermediatesofcellularmetabolismforenzymaticfunction.Furthermore,changestointracellularmetabolismcanaltertheexpressionofspecifichistonemethyltransferasesandacetyltransferasesconferringwidespreadvariationsinepigeneticmodificationpatterns.Specificepigeneticinfluencesofdietaryglucoseandlipidconsumption,aswellasundernutrition,areobservedacrossnumerousorgansandpathwaysassociatedwith...
