Histonemethylation:adynamicmarkinhealth,diseaseandinheritanceEricL.Greer1andYangShi11CellBiologyDepartment,HarvardMedicalSchoolandDivisionofNewbornMedicine,Children’sHospitalBoston,300LongwoodAvenue,Boston,Massachusetts02115,USAAbstractOrganismsrequireanappropriatebalanceofstabilityandreversibilityingeneexpressionprograms,tomaintaincellidentityortoenableresponsestostimuli;epigeneticregulationisintegraltothisdynamiccontrol.Post-translationalmodificationofhistonesbymethylationisanimportantandwidespreadtypeofchromatinmodificationthatisknowntoinfluencebiologicalprocessesinthecontextofdevelopmentandcellularresponses.Weprovideabroadoverviewofhowhistonemethylationisregulatedandleadstobiologicaloutcomes,toevaluatehowhistonemethylationcontributestostableorreversiblecontrol.Theimportanceofmaintainingorreprogramminghistonemethylationappropriatelyisillustratedbylinkstodiseaseandaging,orpossiblytransmissionoftraitsacrossgenerations.IntroductionGeneticinformationencodedinDNAislargelyidenticalineverycellofaeukaryote.Yetcellsindifferenttissuesandorganscanhavewidelydifferentgeneexpressionpatternsandexhibitspecializedfunctions.Geneexpressionpatternsindifferentcelltypesneedtobeappropriatelyinducedandmaintainedandalsotorespondtodevelopmentalandenvironmentalchanges;inappropriateexpressionleadstodisease.Ineukaryotes,thechromatinstate–thepackagingofDNAwithhistoneproteins-isbelievedtocontributetocontrolofgeneexpression.Histonepost-translationalmodifications(PTMs)includephosphorylation,acetylation,ubiquitinylation,methylationandothers1,2,andthesemodificationsarethoughttocontributetocontrolofgeneexpressionthroughinfluencingchromatincompactionorsignalingtootherproteincomplexes.Therefore,anappropriatebalanceofstabilityanddynamicsinhistonePTMsisnecessaryforaccurategeneexpression.Histonemethylationoccursonallbasicresidues:arginines3,lysines4andhistidines5.Lysinescanbemono(me1)4,di(me2)6,ortri(me3)7methylatedontheirεaminegroup,argininescanbemono(me1)3,symmetricallydimethylated(me2s),orasyme...
