HistoneH2AmonoubiquitinationinneurodevelopmentaldisordersAnshikaSrivastava1,BrianMcGrath2,andStephanieL.Bielas1,2,*1DepartmentofHumanGenetics,UniversityofMichiganMedicalSchool,AnnArbor,Michigan,U.S.A2CellandMolecularBiologyProgram,UniversityofMichiganMedicalSchool,AnnArbor,Michigan,U.S.AAbstractCovalenthistonemodificationsplayanessentialroleingeneregulationandcellularspecificationrequiredformulticellularorganismdevelopment.Mono-ubiquitinationofhistoneH2A(H2AUb1)isareversibletranscriptionallyrepressivemark.ExchangeofhistoneH2Amono-ubiquitinationanddeubiquitinationreflectsthesuccessionoftranscriptionalprofilesduringdevelopmentrequiredtoproducecellulardiversityfrompluripotentcells.GermlinepathogenicvariantsincomponentsoftheH2AUb1regulatoryaxisarebeingidentifiedasthegeneticbasisofcongenitalneurodevelopmentaldisorders.Here,wereviewthehumangeneticsfindingscoalescingonmolecularmechanismsthatalterthegenome-widedistributionofthishistonemodificationrequiredfordevelopment.KeywordsHistonemono-ubiquitination;Polycombrepression;neurogenetics;neurodevelopmentdisordersChromatinmodificationsinbraindevelopmentDevelopmentaldecisionsduringlineagecommitmentarepreciselycoordinatedatthegenomelevelbygeneexpressionprogramsthatjointlyactivateorrepresstranscription[1].Braindevelopmentrequirestheconcurrentdifferentiationofneuronalcelltypesthatmustbeorganizedintoacomplexorgan[2,3].Thisprocessinvolvesspecificationofpluripotentcellstoectodermandneuralprecursorspriortoterminaldifferentiation.Thus,braindevelopmentdependsonprecisetemporalcontrolofgeneexpressionpatterns,anddisruptionoftranscriptionalnetworksinbraindevelopmentunderliesneurodevelopmentaldisorders.Itisnotknownhowgroupsofgenesareco-regulatedduringfatespecificationof*CorrespondingAuthor:StephanieL.Bielas,DepartmentofHumanGenetics,UniversityofMichiganMedicalSchool,3703MedicalScienceII,1137CatherineSt.SPC5618,AnnArbor,MI48109-5618,U.S.A.Phone:001.734.647.8890;Fax:011.734.763.3784;sbielas@umich.edu.Publisher'sDisclaimer:ThisisaPDFfileofan...
