RolesandregulationofhistonemethylationinanimaldevelopmentAshwiniJambhekar1,2,3,*,AbhinavDhall1,2,YangShi1,2,*1NewbornMedicine,BostonChildren’sHospital,Boston,MA,USA.2DepartmentofCellBiology,HarvardMedicalSchool,Boston,MA,USA.3DepartmentofSystemsBiology,HarvardMedicalSchool,Boston,MA,USA.AbstractHistonemethylationcanoccuratvarioussitesinhistoneproteins,primarilyonlysineandarginineresidues,anditcanbegovernedbymultiplepositiveandnegativeregulators,evenatasinglesite,toeitheractivateorrepresstranscription.Itisnowapparentthathistonemethylationiscriticalforalmostallstagesofdevelopment,anditsproperregulationisessentialforensuringthecoordinatedexpressionofgenenetworksthatgovernpluripotency,bodypatterninganddifferentiationalongappropriatelineagesandorganogenesis.Notably,developmentalhistonemethylationishighlydynamic.Earlyembryonicsystemsdisplayuniquehistonemethylationpatterns,prominentlyincludingthepresenceofbivalent(bothgene-activatingandgene-repressive)marksatlineage-specificgenesthatresolvetomonovalentmarksduringdifferentiation,whichensuresthatappropriategenesareexpressedineachtissuetype.Studiesoftheeffectsofmethylationonembryonicstemcellpluripotencyanddifferentiationhavehelpedtoelucidatethedevelopmentalrolesofhistonemethylation.Ithasbeenrevealedthatmethylationanddemethylationofbothactivatingandrepressivemarksareessentialforestablishingembryonicandextra-embryoniclineages,forensuringgenedosagecompensationviagenomicimprintingandforestablishingbodypatterningviaHOXgeneregulation.Notsurprisingly,aberrantmethylationduringembryogenesiscanleadtodefectsinbodypatterningandinthedevelopmentofspecificorgans.Humangeneticdisordersarisingfrommutationsinhistonemethylationregulatorshaverevealedtheirimportantrolesinthedevelopingskeletalandnervoussystems,andtheyhighlighttheoverlappinganduniquerolesofdifferentpatternsofmethylationinensuringproperdevelopment.*ashwini_jambhekar@hms.harvard.edu;yang_shi@hms.harvard.edu.AuthorcontributionsAllauthorsmadesubstantialcontributionstothediscussionof...
