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Epigenetic transgenerational inheritance of somatic transcriptomes and epigenetic controlregions.doc

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Epigenetic transgenerational inheritance of somatic transcriptomes and epigenetic controlregions

Skinneretal.GenomeBiology2012,13:R91 /2012/13/10/R91 RESEARCH OpenAccess Epigenetictransgenerationalinheritanceof somatictranscriptomesandepigenetic controlregions MichaelKSkinner1*,MohanManikkam1,MdMHaque1,BinZhang2andMarinaISavenkova1 abstract Background:Environmentallyinducedepigenetictransgenerationalinheritanceofadultonsetdiseaseinvolvesa varietyofphenotypicchanges,suggestingageneralalterationingenomeactivity. Results:InvestigationofdifferenttissuetranscriptomesinmaleandfemaleF3generationvinclozolinversuscontrol lineageratsdemonstratedalltissuesexaminedhadtransgenerationaltranscriptomes.Themicroarraysfrom11 differenttissueswerecomparedwithagenebionetworkanalysis.Althougheachtissuetransgenerational transcriptomewasunique,commoncellularpathwaysandprocesseswereidentifiedbetweenthetissues.Acluster analysisidentifiedgenemoduleswithcoordinatedgeneexpressionandeachhaduniquegenenetworks regulatingtissue-specificgeneexpressionandfunction.Alargenumberofstatisticallysignificantover-represented clustersofgeneswereidentifiedinthegenomeforbothmalesandfemales.Thesegeneclustersrangedfrom2-5 megabasesinsize,andanumberofthemcorrespondedtotheepimutationspreviouslyidentifiedinspermthat transmittheepigenetictransgenerationalinheritanceofdiseasephenotypes. Conclusions:Combinedobservationsdemonstratethatalltissuesderivedfromtheepigeneticallyalteredgerm linedeveloptransgenerationaltranscriptomesuniquetothetissue,butcommonepigeneticcontrolregionsinthe genomemaycoordinatelyregulatethesetissue-specifictranscriptomes.Thissystemsbiologyapproachprovides insightintothemolecularmechanismsinvolvedintheepigenetictransgenerationalinheritanceofavarietyof adultonsetdiseasephenotypes. Background [5-7].Theepigenetictransgenerationalinheritanceofsuch Epigenetictransgenerationalinheritanceinvolvesthegerm abnormalphenotypeshasbeenshowntodevelopinF1to linetransmissionofepigeneticmarksbetweengenerations F4generationsafterenvironmental exposureofonlyan thataltergenomeactivityandphenotype[1-3].En