Interplaybetweenmetabolismandepigenetics:anuclearadaptationtoenvironmentalchangesJean-PierreEtchegaray1,2andRaulMostoslavsky1,2,3,*1TheMassachusettsGeneralHospitalCancerCenter,HarvardMedicalSchool,Boston,Massachusetts02114,USA2TheMGHCenterforRegenerativeMedicine,HarvardMedicalSchool,Boston,Massachusetts02114,USA3TheBroadInstituteofHarvardandMIT,Cambridge,MA02142,USAAbstractThephysiologicalidentityofeverycellismaintainedbyhighlyspecifictranscriptionalnetworksthatestablishacoherentmolecularprogramthatisin-tunewithnutritionalconditions.Theregulationofcell-specifictranscriptionalnetworksisaccomplishedbyanepigeneticprogramviachromatinmodifyingenzymes,whoseactivityisdirectlydependentonmetabolitessuchasacetyl-CoA,S-adenosylmethionineandNAD+amongothers.Therefore,thesenuclearactivitiesaredirectlyinfluencedbythenutritionalstatusofthecell.Inadditiontonutritionalavailability,thishighlycollaborativeprogrambetweenepigeneticdynamicsandmetabolismisfurtherinterconnectedwithotherenvironmentalcuesprovidedbytheday-nightcyclesimposedbycircadianrhythms.Herein,wereviewmolecularpathwaysandtheirmetabolitesassociatedwithepigeneticadaptationsmodulatedbyhistone-andDNA-modifyingenzymesandtheirresponsivenesstotheenvironmentinthecontextofhealthanddisease.INTRODUCTIONEpigeneticsisdefinedbytheheritabletraitsthatdonotinvolvealterationsinDNAsequence,butratherchemicalchangeswithinthechromatin.Thesechemicalchangesentailposttranslationalmodificationsofhistonesproteins,DNAmethylationandDNAoxidationevents.TheinheritanceaspectofepigeneticsismostlyunderstoodwithregardtoDNAmethylation.However,epigeneticsmediatedbyhistonemodificationsremainanopenquestionandanactiveareaofresearch(reviewedinZhuandReinberg,2011).Nevertheless,thesehistonemodificationsdirectlymodulatechromatinstructureandconsequentlyinfluencegeneexpression.Morespecifically,theestablishmentofepigeneticsignaturesisaccomplishedbyspecificsetsofenzymesthataddorremovedifferenttypesofposttranslationalmodificationsincludingacetylormethylgroupstodistinc...
