Theeukaryoticgenomeispackagedbyhistoneandnonhistoneproteinstoformchromatin.Theassemblyofnucleosomesaswellascompactionofnucleosomalarraysintohigher-orderchromatinstructurescreateahighlyrestrictiveenvironmentfornuclearprocessesthatrequireaccesstoDNA.ThepackagingofeukaryoticDNAintonucleosomesinhibitstheaccessoffactorstoDNAandthusresultsintherepressionoftranscription,replication,andrecombination.Tocounterbalancetherepressivenatureofchromatin,avarietyofchromatinremodelingfactorsusetheenergyofATPhydrolysistofacilitatetheinteractionofproteinswithnucleosomalDNA.ATPdependentchromatinremodelingcomplexesarecharacterizedbythepresenceofanATPasesubunitfromSNF2-likefamilyoftheDEAD/H(SF2)DNA-stimulatedATP-ases.ThehighlyconservativehSWI/SNFmultisubunitcomplexescontainhBRMorBRG1ATPaseswhichalterthehistone-DNAcontactsenablingtheaccessofgeneraltranscriptionfactorstopromoterregions.Remodelingcomplexesaretargetedtopromotersviainteractionswithsequence-specifictranscriptionfactors.SincechromatinconstitutesabarrierforprocessesaffectingDNA,suchatranscription,replicationandrepair,amechanismisrequiredthatcanopenuporremodelchromatintomakeitaccessIBLetoreplicationandtranscriptionfactors.Steroidreceptorsareaclassoftranscriptionfactorsthatcaninteractwiththerepressivechromatinstructureandremodelthechromatintoallowothertranscriptionfactorstobind.Inadditiontonuclearreceptors,transcriptionactivatorsasdivergentaserythroidKruppel-likefactor,C/EBP_,c-Myc,MyoD,HSF1,andEBNA2havealsobeenfoundtorecruitSWI/SNFtospecificpromoters.Theroleofsteroidreceptorsinchromatinremodelingandtranscriptionisexemplifiedbytheglucocorticoidreceptor(GR)-mediatedtransactivationofthemousemammarytumorvirus(MMTV)promoter.TheMMTVpromoterisorganizedintoaphasedarrayofsixnucleosomeswhenstablyintegratedintomammaliancells.Thesecondnucleosome(nucB)ispositionedoverthebindingsitesfortheGRandnuclearfactor1(NF1).BindingofNF1isessentialforGR-mediatedtransactivationoftheMMTVpromoter;intheabsenceofglucocorticoid,thechromatinstructureofthepromoterexcludesthebindingofNF1.UponhormoneadmiNISTration,GRrecruitsanATP-dependentremodelinghSWI/SNFcomplex(BRG1-BAF)toremodelthechromatinIndividually,theGRmakesdirectinteractionswithBRG1-associatedfactor60a(BAF60a)andBAF57.Further,BAF60apossessesatleasttwointeractionsurfaces,oneforGRandBRG1andasecondforBAF155andBAF170.TheremodelingprocessconvertstheclosedconformationoftheMMTVpromotertoanopenonewithoutalteringthenucleosomalpositioning.TheremodelingofthepromoterpermitsNF1bindingandtheassemblyofatranscriptioninitiationcomplex.

Contributor:A.Konev,PhD

REFERENCES:HebbarPB,ArcherTK.Nuclearfactor1isrequiredforbothhormone-dependentchromatinremodelingandtranscriptionalactivationofthemousemammarytumorviruspromoter.MolCellBiol.2003(3):887-98.HsiaoPWetal.BAF60aMediatesCriticalInteractionsbetweenNuclearReceptorsandtheBRG1Chromatin-RemodelingComplexforTransactivation.MolCellBiol.2003(17):6210-6220.NarlikarGJetal.Cooperationbetweencomplexesthatregulatechromatinstructureandtranscription.Cell.2002108(4):475-87VignaliMetal.ATP-dependentchromatin-remodelingcomplexes.MolCellBiol.2000(6):1899-910

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