An Unbiased Assessment of the Role of Imprinted Genes in an Intergenerational Model of Developmental Programming 英文参考文献.docVIP

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An Unbiased Assessment of the Role of Imprinted Genes in an Intergenerational Model of Developmental Programming 英文参考文献.doc

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An Unbiased Assessment of the Role of Imprinted Genes in an Intergenerational Model of Developmental Programming 英文参考文献

AnUnbiasedAssessmentoftheRoleofImprintedGenes inanIntergenerationalModelofDevelopmental Programming ElizabethJ.Radford1,ElviraIsganaitis2,JosepJimenez-Chillaron2,JoshuaSchroeder2,MichaelMolla2, SimonAndrews3,NathalieDidier4,MarikaCharalambous1,KirstenMcEwen1,GiovannaMarazzi4, DavidSassoon4,Mary-ElizabethPatti2*,AnneC.Ferguson-Smith1* 1Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom, 2Research Division, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts, United States of America, 3Bioinformatics Group, The Babraham Institute, Cambridge, United Kingdom, 4Myology Group-UMRS787,INSERMandUniversite′ ParisVI/PierreetMarieCurie,Paris,France Abstract Environmentalfactorsduringearlylifearecriticalforthelatermetabolichealthoftheindividualandoffutureprogeny.In ourobesogenicenvironment,itisofgreatsocioeconomicimportancetoinvestigatethemechanismsthatcontributetothe riskofmetabolicillhealth.Imprintedgenes,aclassoffunctionallymono-allelicgenescriticalforearlygrowthandmetabolic axisdevelopment,havebeenproposedtobeuniquelysusceptibletoenvironmentalchange.Furthermore,ithasalsobeen suggested that perturbation of the epigenetic reprogramming of imprinting control regions (ICRs) may play a role in phenotypicheritabilityfollowingearlylifeinsults.Alternatively,thepresenceofmultiplelayersofepigeneticregulationmay in fact protect imprinted genes from such perturbation. Unbiased investigation of these alternative hypotheses requires assessment of imprinted gene expression in the context of the response of the whole transcriptome to environmental assault.Wethereforeanalysetheroleofimprintedgenesinmultipletissuesintwoaffectedgenerationsofanestablished murine model of the developmental origins of health and disease using microarrays and quantitative RT–PCR. We demonstratethat,despitethefunctionalmono-allelicismofimprintedgenesandtheiruniquemechanismsofepigenetic dosage control, imprinted genes as a class are ne