Genetic Variation Stimulated by Epigenetic Modification 英文参考文献.docVIP

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Genetic Variation Stimulated by Epigenetic Modification 英文参考文献.doc

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Genetic Variation Stimulated by Epigenetic Modification 英文参考文献

GeneticVariationStimulatedbyEpigeneticModification W.JasonCummings1,DavidW.Bednarski1,NancyMaizels1,2* 1DepartmentofImmunology,UniversityofWashingtonSchoolofMedicine,Seattle,Washington,UnitedStatesofAmerica,2DepartmentofBiochemistry,Universityof WashingtonSchoolofMedicine,Seattle,Washington,UnitedStatesofAmerica Abstract Homologous recombination is essential for maintaining genomic integrity. A common repair mechanism, it uses a homologousorhomeologousdonorasatemplateforrepairofadamagedtargetgene.Suchrepairmustberegulated,both toidentifyappropriatedonorsforrepair,andtoavoidexcessorinappropriaterecombination.Weshowthatmodifications of donor chromatin structure can promote homology-directed repair. These experiments demonstrate that either the activatorVP16orthehistonechaperone,HIRA,acceleratedgeneconversionapproximately10-foldwhentetheredwithin thedonorarrayforIggeneconversioninthechickenBcelllineDT40.VP16greatlyincreasedlevelsofacetylatedhistones H3andH4,whiletetheredHIRAdidnotaffecthistoneacetylation,butcausedanincreaseinlocalnucleosomedensityand levelsofhistoneH3.3.Thus,epigeneticmodificationcanstimulategeneticvariation.Theevidencethatdistinctactivating modifications can promote similar functional outcomes suggests that a variety of chromatin changes may regulate homologousrecombination,andthatdisregulationofepigeneticmarksmayhavedeleteriousgeneticconsequences. Citation: Cummings WJ, Bednarski DW, Maizels N (2007) Genetic Variation Stimulated by Epigenetic Modification. PLoS ONE 3(12): e4075. doi:10.1371/ journal.pone.0004075 Editor:JamesE.Haber,BrandeisUniversity,UnitedStatesofAmerica ReceivedNovember19,2008;AcceptedNovember30,2008;PublishedDecember30,2008 Copyright: ?2007 Cummingset al.This isan open-access article distributedunder the terms ofthe CreativeCommons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisresearchwasfundedbyNIHR01GM41712andRL1GM084434.The