Dynamic Reprogramming of DNA Methylation at an Epigenetically Sensitive Allele in Mice 英文参考文献.docVIP
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Dynamic Reprogramming of DNA Methylation at an Epigenetically Sensitive Allele in Mice 英文参考文献
DynamicReprogrammingofDNAMethylation
atanEpigeneticallySensitiveAlleleinMice
Marnie E.Blewitt1¤,Nicola K.Vickaryous1,Andras Paldi2,Haruhiko Koseki3,Emma Whitelaw1,4*
1SchoolofMolecularandMicrobialBiosciences,UniversityofSydney,NewSouthWales,Australia,2GenethonandEPHE,Evry,France,3DevelopmentalGeneticsGroup,
RIKENResearchCenterforAllergyandImmunology,Yokohama,Japan,4QueenslandInstituteofMedicalResearch,Brisbane,Queensland,Australia
There is increasing evidence in both plants and animals that epigenetic marks are not always cleared between
generations. Incomplete erasure at genes associated with a measurable phenotype results in unusual patterns of
inheritancefromonegenerationtothenext,termedtransgenerationalepigeneticinheritance.TheAgoutiviableyellow
(Avy)alleleisthebest-studiedexampleofthisphenomenoninmice.TheAvy alleleistheresultofaretrotransposon
insertionupstreamoftheAgoutigene.Expressionatthislocusiscontrolledbythelongterminalrepeat(LTR)ofthe
retrotransposon,andexpressionresultsinayellowcoatandcorrelateswithhypomethylationoftheLTR.Isogenicmice
displayvariableexpressivity,resultinginmicewitharangeofcoatcolours,fromyellowthroughtoagouti.Agoutimice
haveamethylatedLTR.Thelocusdisplaysepigeneticinheritancefollowingmaternalbutnotpaternaltransmission;
yellowmothersproducemoreyellowoffspringthanagoutimothers.WehaveanalysedtheDNAmethylationinmature
gametes, zygotes, and blastocysts and found that the paternally and maternally inherited alleles are treated
differently. The paternally inherited allele is demethylated rapidly, and the maternal allele is demethylated more
slowly,inamannersimilartothatofnonimprintedsingle-copygenes.Interestingly,followingmaternaltransmission
oftheallele,thereisnoDNAmethylationintheblastocyst,suggestingthatDNAmethylationisnottheinheritedmark.
WehaveindependentsupportforthisconclusionfromstudiesthatdonotinvolvedirectanalysisofDNAmethylation.
Haplo-insufficiencyforMel18,apolycombgroupprotein,introducesepigeneticinheritanceatapaternall
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