Condition transition analysis reveals TF activity to nutrient-limitation-specific effects of oxygen presence in yeast

Conference paper (2006)
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2006

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Abstract

Regulatorynetworksareusuallypresentedasgraphstructuresshowingthe(combinatorial)regulatorye¿ectoftranscriptionfactors(TF¿s)onmodulesofsimilarlyexpressedorotherwiserelatedgenes.However,fromthesenetworksitisnotclearwhenandhowTF¿sareactivated.TheactualconditionsorperturbationsthattriggerachangeintheactivityofTF¿sshouldbeacrucialpartofthegeneratedregulatorynetwork.
Here,wedemonstratethepowertouncoverTFactivitybyfocusingonasmall,homogeneous,yetwellde¿nedsetofchemostatcultivationexperiments,wherethetranscriptionalresponseofyeastgrownunderfourdi¿erentnutrientlimitations,bothaerobicallyaswellasanaerobicallywasmeasured.Wede¿neaconditiontransitionasaninstantchangeinyeast¿sextracellularenvironmentbycomparingtwocultivationconditions,whereeitherthelimitednutrientortheoxygenavailabilityisdi¿erent.Di¿erentialgeneexpressionasaconsequenceofsuchaconditiontransitionisrepresentedinatertiarymatrix,wherezeroindicatesnochangeinexpression;1and-1respectivelyindicateanincreaseanddecreaseinexpressionasaconsequenceofaconditiontransition.WeuncoverTFactivitybyassessingsigni¿cantTFbindinginthepromotorregionofgenesthatbehaveaccordinglyataconditiontransition.Theinterrelatednessoftheconditionsinthecombinatorialsetupisexploitedbyperformingspeci¿chypergeometricteststhatallowforthediscoveryofbothindividualandcombinede¿ectsofthecultivationparametersonTFactivity.Additionally,wecreateaweight-matrixindicatingtheinvolvementofeachTFineachoftheconditiontransitionsbyposingourproblemasanorthogonalProcrustesproblem.WeshowthattheProcrustesanalysisstrengthensandbroadenstheuncoveredrelationships.
Theresultingregulatorynetworkrevealsnutrient-limitation-speci¿ce¿ectsofoxygenpresenceonexpressionbehaviorandTFactivity.Ouranalysisidenti¿esmanyTF¿sthatseemtoplayaveryspeci¿cregulatoryroleatthenutrientandoxygenavailabilitytransitions.