Study shows how epigenetic memory is passed across ...

Epigenetic modifications do not affect the DNA sequence of genes, but change how the DNA is packaged and how genes are expressed. Now, a study ... Skiptomaincontent Skiptomainnavigation UCSantaCruz MyUCSC People Calendars Maps A-ZIndex Search Newscenter Awards&Honors Events Videos Subscribe ContactUs HelpfulLinks Newsbytopic Newsarchives E-Newsletter TuesdayNewsday RSSfeeds UCSCMagazine AdministrativeMessages BudgetUpdates Home/2014/September/Studyshowshowepigeneticmemoryispassedacrossgenerations StudyshowshowepigeneticmemoryispassedacrossgenerationsResearcherstracedmarkersofgenerepressionthroughcelldivisionandshowedthatbothspermandeggstransmitamemoryofgenerepressiontoembryosSeptember18,2014 By TimStephensSharethisstory:TwitterFacebookLinkedInRedditImagesofC.elegansembryosshowinheritanceandtransmissionofanepigeneticmark.The1-cellembryo(left)showsthemark(green)inheritedonspermchromosomesbutnotontheoocytechromosomes(pink)fromamutantmotherlackingthemethylationenzymePRC2.The2-cellembryo(right)showstransmissionofthemarkonthesperm-derivedchromosomesineachdaughternucleus.(PhotosbyLauraJ.Gaydos)SusanStrome(photobyC.Lagattuta)Agrowingbodyofevidencesuggeststhatenvironmentalstressescancausechangesingeneexpressionthataretransmittedfromparentstotheiroffspring,making"epigenetics"ahottopic.EpigeneticmodificationsdonotaffecttheDNAsequenceofgenes,butchangehowtheDNAispackagedandhowgenesareexpressed.Now,astudybyscientistsatUCSantaCruzshowshowepigeneticmemorycanbepassedacrossgenerationsandfromcelltocellduringdevelopment. Thestudy,publishedSeptember19inScience,focusedononewellstudiedepigeneticmodification--themethylationofaDNApackagingproteincalledhistoneH3.Methylationofaparticularaminoacid(lysine27)inhistoneH3isknowntoturnoffor"repress"genes,andthisepigeneticmarkisfoundinallmulticellularanimals,fromhumanstothetinyroundwormC.elegansthatwasusedinthisstudy. Ongoingdebate "Therehasbeenongoingdebateaboutwhetherthemethylationmarkcanbepassedonthroughcelldivisionsandacrossgenerations,andwe'venowshownthatitis,"saidcorrespondingauthorSusanStrome,aprofessorofmolecular,cellanddevelopmentalbiologyatUCSantaCruz. Strome'slabcreatedwormswithamutationthatknocksouttheenzymeresponsibleformakingthemethylationmark,thenbredthemwithnormalworms.Usingfluorescentlabels,theywereabletotrackthefatesofmarkedandunmarkedchromosomesunderthemicroscope,fromeggcellsandspermtothedividingcellsofembryosafterfertilization.Embryosfrommutanteggcellsfertilizedbynormalspermhadsixmethylatedchromosomes(fromthesperm)andsixunmarkedor"naked"chromosomes(fromtheegg). Asembryosdevelop,thecellsreplicatetheirchromosomesanddivide.Theresearchersfoundthatwhenamarkedchromosomereplicates,thetwodaughterchromosomesarebothmarked.Butwithouttheenzymeneededforhistonemethylation,themarksbecomeprogressivelydilutedwitheachcelldivision. "Themarkstaysonthechromosomesderivedfromtheinitialchromosomethathadthemark,butthere'snotenoughmarkforbothdaughterchromosomestobefullyloaded,"Stromesaid."Sothemarkisbrightinaone-cellembryo,lessbrightafterthecelldivides,dimmerstillinafour-cellembryo,andbyabout24to48cellswecan'tseeitanymore." Theresearchersthendidtheconverseexperiment,fertilizingnormaleggcellswithmutantsperm.Themethylationenzyme(calledPRC2)isnormallypresentineggcellsbutnotinsperm,whichdon'tcontributemuchmorethantheirchromosomestotheembryo.Sotheembryosinthenewexperimentstillhadsixnakedchromosomes(thistimefromthesperm)andsixmarkedchromosomes,butnowtheyalsohadtheenzyme. "Remarkably,whenwewatchthechromosomesthroughcelldivisions,themarkedchromosomesremainmarkedandstaybright,becausetheenzymekeepsrestoringthemark,butthenakedchromosomesstaynaked,divisionafterdivision,"Stromesaid."Thatshowsthatthepatternofmarksthatwasinheritedisbeingtransmittedthroughmultiplecelldivisions." Importantimplications StromenotedthatthefindingsinthisstudyoftransmissionofhistonemethylationinC.eleganshaveimportantimplicationsinotherorganisms,eventhoughdifferentorganismsusetherepressivemarkerthatwasstudiedtoregulatedifferentgenesduringdifferentaspectsofdevelopment.Allanimalsusethesameenzymetocreatethesamemethylationmarkasasignalforgenerepression,andhercolleagueswhostudyepigeneticsinmiceandhumansareexcitedaboutthenewfindings,Stromesaid. "Transgenerationalepigeneticinheritanceisnotasolvedfield--it'sverymuchinflux,"shesaid."Therearedozensofpotentialepigeneticmarkers.Instudiesthatdocumentparent-to-childepigeneticinheritance,it'snotclearwhat'sbeingpassedon,andunderstandingitmolecularlyisverycomplicated.Wehaveaspecificexampleofepigeneticmemorythatispassedon,andwecanseeitinthemicroscope.It'sonepieceofthepuzzle." ThefirstauthoroftheSciencepaperisLauraGaydos,agraduatestudentinStrome'slabatUCSantaCruzwholedthestudyforherPh.D.thesisandisnowapostdoctoralresearcheratFredHutchinsonCancerResearchCenterinSeattle.TheothercoauthorisWenchaoWang,whodidoneoftheinitialexperimentsasagraduatestudentinStrome'slabseveralyearsagowhenshewasatIndianaUniversity.ThisresearchwassupportedbytheNationalInstitutesofHealth,aUCSCDissertationYearFellowship,andtheARCSFoundation.Sharethisstory:TwitterFacebookLinkedInReddit UniversityNews UniversityNewsHome MonthlyNewsletter OtherNews&Events CampusCalendars UCNews Features UCSantaCruzMagazine Resources AdministrativeMessages UCSCChancellor PressReleases ContactsforReporters Sendusanemail UCSantaCruz,1156HighStreet,SantaCruz,Ca95064 ©2022RegentsoftheUniversityofCalifornia.AllRightsReserved. Feedback Accreditation Non-Discrimination Policy LandAcknowledgement Employment Privacy Policy & Terms of Use SexualViolencePrevention&Response(TitleIX) Lastmodified:September18,2014128.114.113.87