PausereleaseProductiveelongationModesofP-TEFbRecruitment:TFs(e.g.,MYC,NF-κB)Mediator(Med26subunitorCdk8module)AcetylatedhistonesandBrd4OtherelongationfactorsaspartofthesuperelongationcomplexCREDNA-bindingtranscriptionfactors(TFs)associatewithcis-regulatoryelements(CRE)topromoteassemblyofthePIC.TFscanstimulatePICformationdirectlythroughinteractionswiththeMediatorcomplexandhelprecruitthegeneraltranscriptionfactors(GTFs).TFsalsorecruitcoactivatorsthatcanremovenucleosomesfromthepromoterormodifyhistoneproteins,forexamplebyacetylation(Ac)ormethylation(Me).Mediator5´TranscriptionstartsiteAftera20–60ntRNAhasbeensynthesized,pause-inducingfactorsDSIFandNELFbindtheearlyelongationcomplex,inhibitingfurthertranscription.Thedurationofpausingdependsontherateofrecruitmentoffactorsthattriggerpauserelease,whichisvariablefromgenetogeneandunderdifferentcellconditions.CEThePolIIC-terminaldomain(CTD)iscomprisedofmanyrepeatsofthesequenceY1S2P3T4S5P6S7thatundergoposttranslationalmodifcationsduringthetranscriptioncyclebutaregenerallyunmodifedinthePIC.Thecappingenzymecomplex(CE)addsaprotective5´captothenascentRNA.CErecruitmentisstimulatedbyitsinteractionswithDSIFandS5-phosphorylatedCTD.TheGTFcomponentTFIIHcontainsthekinaseCdk7,whichphosphorylatesthePolIICTDattheS5andS7residues.ReleaseofpausedPolIIistriggeredbythekinaseP-TEFb,whichphosphorylatespause-inducingfactorstodissociateNELFandpromoteproductiveelongation.FollowingphosphorylationbyP-TEFb,DSIFhelpsrecruitfactorsthatstimulateproductiveelongation.Thesefactors(e.g.,Paf1c)enhancetherateorprocessivityofRNAsynthesis.NucleosomeCTDTranscriptionthroughnucleosomesandtheireffcientreassemblyinthewakeoftranscribingPolIIarefacilitatedbyhistonechaperoneslikeFACTandSpt6.InitiationofRNAsynthesisrequirestheATP-dependentopeningoftheDNAstrandsbytheTFIIHhelicase.ThePolIICTDisalsophosphorylatedatS2byP-TEFbandthekinaseCdk12/cyclinK,creatingabindingplatformforfactorsthataidinRNAprocessingandtranscriptionthroughchromatin.CRETFCRECRE5´CEThecappingenzymecom...
