A Screen for Retrotransposed Imprinted Genes Reveals an Association between X Chromosome Homology and Maternal Germ-Line Methylation 英文参考文献.docVIP

AScreenforRetrotransposedImprintedGenes RevealsanAssociationbetweenXChromosome HomologyandMaternalGerm-LineMethylation Andrew J.Wood1,Roland G.Roberts1,David Monk2,Gudrun E.Moore2,Reiner Schulz1,Rebecca J.Oakey1* 1 Department of Medical and Molecular Genetics, King’s College London, London, United Kingdom, 2 Unit of Clinical and Molecular Genetics, Institute of Child Health, London,UnitedKingdom Imprinted genes undergo epigenetic modifications during gametogenesis, which lead to transcriptional silencing of eitherthematernallyorthepaternallyderivedalleleinthesubsequentgeneration.Previousworkhassuggestedan associationbetweenimprintingandtheproductsofretrotransposition,butthenatureofthislinkisnotwelldefined.In themouse,threeimprintedgeneshavebeendescribedthatoriginatedbyretrotranspositionandoverlapCpGislands whichundergomethylationduringoogenesis.Nap1l5,U2af1-rs1,andInpp5f_v2arelikelytoencodeproteinsandshare two additional genetic properties: they are located within introns of host transcripts and arederived from parental genesontheXchromosome.Usingthesesequencefeaturesalone,weidentifiedMcts2,anovelcandidateimprinted retrogene on mouse Chromosome 2. Mcts2 has been validated as imprinted by demonstrating that it is paternally expressed and undergoes promoter methylation during oogenesis. The orthologous human retrogenes NAP1L5, INPP5F_V2, and MCTS2 are also shown to be paternally expressed, thus delineating novel imprinted loci on human Chromosomes4,10,and20.ThestrikingcorrelationbetweenimprintingandXchromosomeprovenancesuggeststhat retrotransposed elements with homology to the X chromosome can be selectively targeted for methylation during mammalianoogenesis. Citation: Wood AJ,Roberts RG,Monk D,Moore GE,Schulz R, etal. (2007) Ascreen for retrotransposedimprintedgenesrevealsanassociation betweenX chromosome homologyandmaternalgerm-linemethylation.PLoSGenet3(2):e20.doi:10.1371/journal.pgen.0030020 refer to these putatively functional elements [10–12], as distinc