Multistable Decision Switches for Flexible Control of Epigenetic Differentiation 英文参考文献.docVIP

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Multistable Decision Switches for Flexible Control of Epigenetic Differentiation 英文参考文献.doc

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Multistable Decision Switches for Flexible Control of Epigenetic Differentiation 英文参考文献

MultistableDecisionSwitchesforFlexibleControlof EpigeneticDifferentiation Rau′lGuantes1,2,JuanF.Poyatos3* 1DepartmentofCondensedMatterPhysics,FacultaddeCienciasC-XVI,UniversidadAuto′nomadeMadrid,Madrid,Spain,2InstitutoNicola′sCabrera,FacultaddeCiencias C-XVI, Universidad Auto′noma de Madrid, Madrid, Spain, 3Logic of Genomic Systems Laboratory, Spanish National Biotechnology Centre, Consejo Superior de InvestigacionesCientificas,Madrid,Spain Abstract It is now recognized that molecular circuits with positive feedback can induce two different gene expression states (bistability)undertheverysamecellularconditions.Whether,andhow,cellsmakeuseofthecoexistenceofalargernumber ofstablestates(multistability)ishoweverlargelyunknown.Here,wefirstexaminehowautoregulation,acommonattribute ofgeneticmasterregulators,facilitatesmultistabilityintwo-componentcircuits.Asystematicexplorationofthesemodules’ parameter space reveals two classes of molecular switches, involving transitions in bistable (progression switches) or multistable (decision switches) regimes. We demonstrate the potential of decision switches for multifaceted stimulus processing,includingstrength,duration,andflexiblediscrimination.Thesetasksenhanceresponsespecificity,helptostore short-term memories of recent signaling events, stabilize transient gene expression, and enable stochastic fate commitment.Therelevanceofthesecircuitsisfurthersupportedbybiologicaldata,becausewefindtheminnumerous developmental scenarios. Indeed, many of the presented information-processing features of decision switches could ultimatelydemonstrateamoreflexiblecontrolofepigeneticdifferentiation. Citation: Guantes R, Poyatos JF (2008) Multistable Decision Switches for Flexible Control of Epigenetic Differentiation. PLoS Comput Biol 4(11): e1000235. doi:10.1371/journal.pcbi.1000235 Editor:SatoruMiyano,UniversityofTokyo,Japan ReceivedApril22,2008;AcceptedOctober17,2008;PublishedNovember28,2008 Copyright:?2008Guantes,Poyatos.Thisisanopen-accessar