遗传信息表达的调控.ppt

第63页，课件共99页，创作于2023年2月 5-aza-2′-deoxycytidine(5-azaCdR),aninhibitorofDNAmethylation,第64页，课件共99页，创作于2023年2月第65页，课件共99页，创作于2023年2月第66页，课件共99页，创作于2023年2月HypomethylationofDNAhasmechanistic

implicationsFirst,itcanleadtogeneactivation.Second,acellular‘methylatorphenotype’hasbeenlinkedtomismatchrepair,firstbyLengauerandcolleagues,whoshowedthatcancercellsthataredeficientinDNAmismatchrepairsilencedretroviralconstructpromotersbyDNAmethylation.Third,EhrlichandcolleaguesrecentlylinkedtumourhypomethylationincancertochromosomalinstabilityFourth,hypomethylationisamechanismofdrug,toxinandviraleffectsincancer.Acommonpolymorphismofmethylenetetrahydrofolatereductase(MTHFR),whichisinvolvedinbiosynthesisofthemethylationprecursorS-adenosylmethionine第67页，课件共99页，创作于2023年2月 First,ATP-dependentDNAhelicasesoftheSNF2family—thecatalyticcomponentsofSWI/SNFchromatin-remodellingcomplexes—areessentialformaintainingnormalDNAmethylation.IndividualswiththedevelopmentaldisorderATRX(α-thalassaemia,myelodysplasia)havemutationsintheATRXgene,whichencodesaSNF2-familyhelicase. AsecondchromatinproteinthathasbeenlinkedtohypomethylationandcancerwasrecentlyidentifiedbyMueggeandcolleagues,whofoundthatLsh,aSNF2-familymember,isrequiredformaintenanceofnormalmethylation.第68页，课件共99页，创作于2023年2月Box2|AnXconnectionInthebackgroundofthediscoveriesthatlinkCpG-islandmethylationandgeneinactivationisalargebodyofimportantcorrelativeandmechanisticdatathatarerelatedtoXchromosomeinactivation.Forexample,anearlycluetoaroleingenesilencingcamefromstudiesofMohandasetal.,whoshowedin1981that5-aza-2′-deoxycytidine(5-azaCdR),aninhibitorofDNAmethylationcouldreactivatetheinactiveXchromosome176.ThediscoveryofthefunctionalsignificanceofwhatarenowtermedCpGislandsalsocamefromstudi