Reconstruction of the Core and Extended Regulons of Global Transcription Factors 英文参考文献.docVIP

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Reconstruction of the Core and Extended Regulons of Global Transcription Factors 英文参考文献.doc

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Reconstruction of the Core and Extended Regulons of Global Transcription Factors 英文参考文献

ReconstructionoftheCoreandExtendedRegulonsof GlobalTranscriptionFactors YannS.Dufour1,2,PatriciaJ.Kiley3,TimothyJ.Donohue1* 1DepartmentofBacteriology,UniversityofWisconsin–Madison,Madison,Wisconsin,UnitedStatesofAmerica,2BACTERInstitute,UniversityofWisconsin–Madison, Madison,Wisconsin,UnitedStatesofAmerica,3DepartmentofBiomolecularChemistry,UniversityofWisconsin–Madison,Madison,Wisconsin,UnitedStatesofAmerica Abstract Theprocessesunderlyingtheevolutionofregulatorynetworksareunclear.Toaddressthisquestion,weusedacomparative genomicsapproachthattakesadvantageofthelargenumberofsequencedbacterialgenomestopredictconservedand variable members of transcriptional regulatory networks across phylogenetically related organisms. Specifically, we developedacomputationalmethodtopredicttheconservedregulonsoftranscriptionfactorsacrossa-proteobacteria.We focusedontheCRP/FNRsuper-familyoftranscriptionfactorsbecauseitcontainsseveralwell-characterizedmembers,such asFNR,FixK,andDNR.WhileFNR,FixK,andDNRareeachproposedtoregulatedifferentaspectsofanaerobicmetabolism, they are predicted to recognize very similar DNA target sequences, and they occur in various combinations among individuala-proteobacterialspecies.Inthisstudy,thecompositionoftherespectiveFNR,FixK,orDNRconservedregulons across87a-proteobacterialspecieswaspredictedbycomparingthephylogeneticprofilesoftheregulatorswiththeprofiles ofputativetargetgenes.TheutilityofourpredictionswasevaluatedbyexperimentallycharacterizingtheFnrLregulon(a FNR-type regulator) in the a-proteobacterium Rhodobacter sphaeroides. Our results show that this approach correctly predictedmanyregulonmembers,providednewinsightsintothebiologicalfunctionsoftherespectiveregulonsforthese regulators,andsuggestedmodelsfortheevolutionofthecorrespondingtranscriptionalnetworks.Ourfindingsalsopredict that,atleastfortheFNR-typeregulators,thereisacoresetoftargetgenesconservedacrossmanyspecies.Inaddition,the membersoftheso-calledextendedregulonsfortheFNR-typeregulatorsvarye