dBre1/dSet1-dependent pathway for histone H3K4 trimethylation has essential roles in controlling germline stem cell maintenance and germ cell differentiation in the Drosophila ovary

摘要

TheemDrosophila/emovariangermlinestemcells(GSCs)constantlyexperienceself-renewalanddifferentiation,ensuringthefemalefertilitythroughoutlife.ThebalancebetweenGSCself-renewalanddifferentiationisexquisitelyregulatedbythestemcellniche,thestemcellsthemselvesandsystemicfactors.IncreasingevidencehasshownthattheGSCregulationalsoinvolvesepigeneticmechanismsincludingchromatinremodelingandhistonemodification.Here,wefindthatdBre1,anE3ubiquitinligase,functionsincontrollingGSCself-renewalandgermcelldifferentiationviadistinctmechanisms.RemovalorknockdownofdBre1functioninthegermlineorsomaticnichecelllineageleadstoagradualGSClossanddisruptionofH3K4trimethylationintheemDrosophila/emovary.FurtherstudiessuggestthatthedefectiveGSCmaintenanceisattributabletocompromisedBMPsignalingemittedfromthestemcellnicheandimpairedadhesionofGSCstotheirniche.Ontheotherhand,emdBre1-RNAi/emexpressioninescortcellscausesalossofH3K4trimethylationandaccumulationofspectrosome-containingsinglegermcellsinthegermarium.Reducingemdpp/emoremdally/emlevelssuppressesthegermcelldifferentiationdefects,indicatingthatdBre1limitsBMPsignalingactivitiesforthedifferentiationcontrol.Strikingly,allphenotypesobservedinemdBre1/emmutantovariescanbemimickedbyRNAi-basedreducedexpressionofdSet1,aemDrosophila/emH3K4trimethylase.Moreover,geneticstudiesfavorthatemdBre1/eminteractswithemdSet1/emincontrollingGSCmaintenanceandgermcelldifferentiation.Takentogether,weidentifyadBre1/dSet1-dependentpathwayfortheH3K4methylationinvolvedinthecellfateregulationintheemDrosophila/emovary./p/div