On the Track of DNA Methylation An Interview with Adrian Bird 英文参考文献.docVIP

Interview OntheTrackofDNAMethylation:AnInterviewwith AdrianBird JaneGitschier* DepartmentsofMedicineandPediatrics,InstituteforHumanGenetics,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica Thedayschoolletoutforthesummer, my daughter and I packed our bags for Britain, where we had lived for a few months in 2006. Annie was eager to reconnect with her friends there, and I hadarrangedtoconductthreeinterviews. Indesperationandwiththeclockticking,I struggledtofitmybulkyrecorderintomy wheelie when it dawned on me that the ‘‘talk app’’ on my daughter’s iphone shouldbeuptothejob.Youcanimagine thereluctanceandskepticism onthepart ofmy15-year-old,butshemanagedtoget intothespiritandacquiesced. First up on my schedule was Adrian Bird (Image 1), who holds the Buchanan Chair of Genetics at the University of Edinburgh and is also Director of the Wellcome Trust Centre for Cell Biology. Long before the word ‘‘epigenome’’ was coined, Bird began mapping the distribu- tionofDNAmethylation(occurringatthe cytosine of CpG dinucleotides) in the genomesofavarietyofspecies.Hiswork emerged just as agarose gels, restriction enzymes, and Southern blots were being developed.Birdlaterspawnedtheideaof CpG islands, pockets of DNA rich in unmethylatedCpGsandfrequentlyfound in conjunction with the promoter regions of mammalian genes. Bird’s observation provided a roadmap for disease gene discoveryforabout15years,untilhuman genomedraftsequencesbegantoemerge. Bird’s laboratory then went on to identifyproteinsthatboundtomethylated DNA,oneofwhich(MeCP2)wasdiscov- ered years later to be defective in Rett Syndrome, a rare X-linked disorder in whichaffected girlsdevelopautismanda distinctivesetofbehaviors.Thisastonish- ingturnofeventspropelledBirdtoextend hisstudiesonMeCP2toamurinemodel forRettSyndrome,usheringinnewideas about therapy for this devastating illness, but still leaving open the question of MeCP2’sroleinthebrain. Image1.AdrianBird. doi:10.1371/journal.pge