Promoter-Wide Hypermethylation of the Ribosomal RNA Gene Promoter in the Suicide Brain 英文参考文献.docVIP

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Promoter-Wide Hypermethylation of the Ribosomal RNA Gene Promoter in the Suicide Brain 英文参考文献.doc

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Promoter-Wide Hypermethylation of the Ribosomal RNA Gene Promoter in the Suicide Brain 英文参考文献

Promoter-WideHypermethylationoftheRibosomalRNA GenePromoterintheSuicideBrain PatrickO.McGowan1,2,3,AyaSasaki1,2,3,TonyC.T.Huang3,4,AlexanderUnterberger3,4 ,Matthew Suderman3,5,CarlErnst1,6,MichaelJ.Meaney1,2,3,GustavoTurecki1,6*,MosheSzyf3,4 * 1DepartmentofPsychiatry,DouglasMentalHealthUniversityInstitute,Montreal,Quebec,Canada,2DepartmentofNeurologyandNeurosurgery,McGillProgramforthe StudyofBehaviour,GenesandEnvironment,McGillUniversity,Montreal,Quebec,Canada,3SacklerProgramforEpigeneticsPsychobiology,McGillUniversity,Montreal, Quebec, Canada, 4Department of Pharmacology and Therapeutics, McGill University, Montreal,Quebec, Canada, 5McGill Centre for Bioinformatics, McGill University, Montreal,Quebec,Canada,6McGillGroupforSuicideStudies,DouglasMentalHealthUniversityInstitute,Montreal,Quebec,Canada Abstract Background: Alterations in gene expression in the suicide brain have been reported and for several genes DNA methylationasanepigeneticregulatoristhoughttoplayarole.rRNAgenes,thatencoderibosomalRNA,arethebackbone oftheproteinsynthesismachineryandlevelsofrRNAgenepromotermethylationdeterminerRNAtranscription. Methodology/PrincipalFindings:WetestherebysodiumbisulfitemappingoftherRNApromoterandquantitativereal- time PCR of rRNA expression the hypothesis that epigenetic differences in critical loci in the brain are involved in the pathophysiology of suicide. Suicide subjects in this study were selected for a history of early childhood neglect/abuse, which is associated with decreased hippocampal volume and cognitive impairments. rRNA was significantly hypermethylated throughout the promoter and 59 regulatory region in the brain of suicide subjects, consistent with reducedrRNAexpressioninthehippocampus.ThisdifferenceinrRNAmethylationwasnotevidentinthecerebellumand occurredintheabsenceofgenome-widechangesinmethylation,asassessedbynearestneighbor. Conclusions/Significance: This is the first study to show aberrant regulation of the protein synthesis machinery in the