Thechromatinpackagingofthegenomeisdynamic,changingwiththecellcycleandwithtranscriptionalregulation.Duringmitosis,chromatiniscondensedforsegregationofchromosomes,whilefortranscriptionchromatinismoreopen.Thenuclearmatrix,orscaffold,isaproteinnetworkinthenucleusprovidingstructureandregulatingchromatincondensation.Regulatedinteractionsofmatrixproteinswitheachother,DNAandotherfactorsindifferentphasesofthecellcyclealterthestructureandfunctionofchromatin.AKAP95(A-kinaseanchoringprotein)isanuclearmatrixassociatedproteinthatalsobindsDNAanddifferentproteinsduringdifferentphasesofthecellcycle.TheinteractionofAKAP95withDNAandproteinsaltersthecondensationandtranscriptionofchromatin.AspecificdomainofAKAP95regulatesitsinteractionwiththenuclearmatrixandanotherregulatesitsassociationwithDNA.OnekeyproteinthatAKAP95interactswithisthecAMP-dependentproteinkinase,PKA.AKAP95bindstoPKAthroughaPKARIIregulatorysubunit,aninteractionthatrequiresPKAphosphorylationbyCdk1.PKAactivityandcAMParereducedduringentryintomitosis,butPKArecruitedbyAKAP95tocondensedchromosomesisessentialtomaintainthecondensedstate.AnotherproteinrecruitedbyAKAP95isEg7,a150kDproteinrecruitedduringmitoticchromatincondensation.Eg7isapartofamultiproteincondensincomplex,recruitinganotherkeycomponentofmitoticchromatincondensation.Modificationofthecorehistonesthroughphosphorylationregulateschromatincondensation.HistoneH3interactswiththecondensincomplex,andisphosphorylatedduringmitosis.HistoneH3phosphorylationbyAurora-2induceschromatincondensation,anddephosphorylationbyPP1promoteschromatindecondensationforreentryintointerphase.AKAP95mayplayaroleduringtheregulationofchromatinstructurefortranscriptionduringinterphaseaswell.TheinteractionofAKAP95withthep68RNAhelicaserecruitsthisenzymetothenuclearmatrixduringinterphase.OthernuclearRNAhelicasesinteractwithtranscriptionfactorsandcofactors,suggestingthatthep68RNAhelicasealsomayregulateinteractionsoftranscriptioncomplexes.

Contributor:KosiGramatikoff

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