Genome-Wide Integration on Transcription Factors, Histone Acetylation and Gene Expression Reveals Genes Co-Regulated by Histone Modification Patterns 英文参考文献.docVIP

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Genome-Wide Integration on Transcription Factors, Histone Acetylation and Gene Expression Reveals Genes Co-Regulated by Histone Modification Patterns 英文参考文献.doc

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Genome-Wide Integration on Transcription Factors, Histone Acetylation and Gene Expression Reveals Genes Co-Regulated by Histone Modification Patterns 英文参考文献

Genome-WideIntegrationonTranscriptionFactors, HistoneAcetylationandGeneExpressionRevealsGenes Co-RegulatedbyHistoneModificationPatterns YayoiNatsume-Kitatani1,2¤,MotokiShiga1,2,HiroshiMamitsuka1,2 * 1BioinformaticsCenter,InstituteforChemicalResearch,KyotoUniversity,Gokasho,Uji,Japan,2InstituteforBioinformaticsResearchandDevelopmentofJapanScience andTechnologyAgency(JST-BIRD),Saitama,Japan Abstract N-terminaltailsofH2A,H2B,H3andH4histonefamiliesaresubjectedtoposttranslationalmodificationsthattakepartin transcriptionalregulationmechanisms,suchastranscriptionfactorbindingandgeneexpression.Regulationmechanisms under control of histone modification are important but remain largely unclear, despite of emerging datasets for comprehensiveanalysisofhistonemodification.Inthispaper,wefocusonwhatwecallgeneticharmoniousunits(GHUs), whichareco-occurringpatternsamongtranscriptionfactorbinding,geneexpressionandhistonemodification.Wepresent thefirstgenome-wideapproachthatcapturesGHUsbycombiningChIP-chipwithmicroarraydatasetsfromSaccharomyces cerevisiae. Our approach employs noise-robust soft clustering to select patterns which share the same preferences in transcription factor-binding, histone modification and gene expression, which are all currently implied to be closely correlated. The detected patterns are a well-studied acetylation of lysine 16 of H4 in glucose depletion as well as co- acetylationoffivelysineresiduesofH3withH4Lys12andH2ALys7responsibleforribosomebiogenesis.Furthermore,our methodfurthersuggestedtherecognitionofacetylatedH4Lys16beingcrucialtohistoneacetyltransferaseESA1,whose essentialroleisstillundercontroversy,fromamicroarraydatasetonESA1anditsbypasssuppressormutants.Theseresults demonstratethatourapproachallowsustoprovideclearerprinciplesbehindgeneregulationmechanismsunderhistone modifications and detect GHUs further by applying to other microarray and ChIP-chip datasets. The source code of our method,whichwasimplementedinMATLAB(/),isavailablefromthesupportin