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1、LeadingEdgeReviewImpulseControl:TemporalDynamicsinGeneTranscriptionNirYosef1,2andAvivRegev1,3,*1BroadInstituteofMITandHarvard,7CambridgeCenter,Cambridge,MA02142,USA2CenterforNeurologicDiseases,Brigham&WomensHospital,HarvardMedicalSchool,Boston,MA02115,USA3HowardHughesMedical
2、Institute,DepartmentofBiology,MassachusettsInstituteofTechnology,Cambridge,MA02139,USA*Correspondence:aregev@broad.mit.eduDOI10.1016/j.cell.2011.02.015Regulatorycircuitscontrollinggeneexpressionconstantlyrewiretoadapttoenvironmentalstimuli,differentiationcues,anddisease.Were
3、viewourcurrentunderstandingofthetemporaldynamicsofgeneexpressionineukaryotesandprokaryotesandthemolecularmechanismsthatshapethem.Wedelineateseveralprototypicaltemporalpatterns,including‘‘impulse’’(orsingle-pulse)patternsinresponsetotransientenvironmentalstimuli,sustained(ors
4、tate-transitioning)patternsinresponsetodevelopmentalcues,andoscillatingpatterns.Wefocusonimpulseresponsesandtheirhigher-ordertemporalorganizationinregulonsandcascadesanddescribehowcoreproteincircuitsandcis-regulatorysequencesinpromotersintegratewithchromatinarchitecturetogen
5、eratetheseresponses.Introductiontotransformourabilitytomanipulatecellularinputsandcompo-Thetranscriptionalprogramthatcontrolsgeneexpressioninnentsatunparalleledtemporalresolution.cellsandorganismsisremarkablyflexible,constantlyreconfi-Here,wereviewrecentadvancesinourunderstand
6、ingoftran-guringitselftorespondandadapttoperturbations.Thesescriptionaldynamics,includingtheprototypicalpatternsofchangesareapparentacrossabroadrangeoftimescales,temporalmRNAexpressionandtheirunderlyingmolecularfromrapidresponsestoenvironmentalsignals(i.e.,minutestomechanism
7、s.Weidentifyasmallnumberofprominenttemporalhours)toslowereventsduringdevelopmentandpathogenesispatterns,suchassinglepulseresponses(impulses),sustained(i.e.,hourstodays)(Lopez-Mauryetal.,2008).state-transitioningpatterns,andoscillations.FocusingonDissectingthesedynamicchanges
8、,bothfunctionallyandimpulseresponses,wethenpresentthemolecularcircuitsthatm
