Followingactivationbyantigen-presentingcells,naiveCD4+TcellsdifferentiateintovariousThelper(TH)cellsubsetsdependingonthenatureoftheantigenicstim-ulusandthecytokinemicroenvironmentatthesiteofantigenrecognition.EachTHcelllineageischaracter-izedbyasetofkeytranscriptionfactorsandlineage-specificgeneexpressionpatterns,includingdistinctcytokineexpressionprofiles,althoughTHcellsubsetlineageidentityisnotfixed,andplasticityofTHcellshasbeendemonstrated.Thus,duringTHcelllineagedifferentiation,cellfatedecisionsaremadeandlineage-specificgeneexpressionprogrammesareestablishedandmaintained.Inadditiontodedicatedtranscriptionalregulators,epigeneticmechanisms,suchaschromatinmodifications,playcrucialrolesintheseprocesses.Lysineacetylationisoneofthebest-studiedhistonemodifications,anditreducesnucleosomaloccupancyofDNA,therebycreatingatranscriptionallypermissivechromatinstructure.Reversiblehistoneacetylationatlysineresiduesiscontrolledbyhistoneacetyltransferases(HATs)andhistonedeacetylases(HDACs),whicharecon-sideredtranscriptionalco-activatorsandco-repressors,respectively.However,HATsandHDACstargetnotonlyhistonesbutalsomanynon-histoneproteins,and,there-fore,theyarealsoreferredtoaslysineacetyltransferases(KATs)andlysinedeacetylases(KDACs).Theacetylationstatusofnon-histonetargetsreg-ulatestheiractivityandfunction,and,thus,lysineacetylationisanimportantpost-translationalmodifica-tion(PTM)thatregulatesavarietyofcellularpathways(whichalsooccursinatissue-specificmanner1)andislikelytobecomparabletootherPTMssuchasproteinphosphorylation2,3.Furthermore,HDACinhibitorsareusedclinicallyforthetreatmentofcertaintypesofhae-matologicalmalignancies,andpreclinicalanimalmodelsindicatethatHDACinhibitorsmightalsohavepotentialastherapiesforTcell-mediateddiseases.InthisReview,weprovideanoverviewofthecontrolofCD4+TcellimmunitybymembersoftheHDACfamily.Wefirstsummarizethebasicprinciplesandknownfunc-tionsofHDACsashistonemodifiersandhighlightthatHDACsalsotargetmanynon-histoneproteins,atraitthathasanimportantimpa...
