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Global Analysis of the Relationship between JIL-1 Kinase and Transcription 英文参考文献.docVIP

Global Analysis of the Relationship between JIL-1 Kinase and Transcription 英文参考文献.doc

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Global Analysis of the Relationship between JIL-1 Kinase and Transcription 英文参考文献

GlobalAnalysisoftheRelationshipbetweenJIL-1Kinase andTranscription CatherineRegnard,TobiasStraub,AngelikaMitterweger,InaK.Dahlsveen,ViolaFabian,PeterB. Becker* Adolf-Butenandt-InstituteandCentreforIntegratedProteinScience(CiPSM),Ludwig-Maximilians-University,Munich,Germany Abstract TheubiquitoustandemkinaseJIL-1isessentialforDrosophiladevelopment.Itsroleindefiningdecondenseddomainsoflarval polytenechromosomesiswellestablished,butitsinvolvementintranscriptionregulationhasremainedcontroversial.Fora firstcomprehensivemolecularcharacterisationofJIL-1,wegeneratedahigh-resolution,chromosome-wideinteractionprofile ofthekinaseinDrosophilacellsanddetermineditsroleintranscription.JIL-1bindsactivegenesalongtheirentirelength.The presence of the kinase is not proportional to average transcription levels or polymerase density. Comparison of JIL-1 associationwithelongatingRNApolymeraseandavarietyofhistonemodificationssuggeststwodistincttargetingprinciples. AbasallevelofJIL-1bindingcanbedefinedthatcorrelatesbestwiththemethylationofhistoneH3atlysine36,amarkthatis placedco-transcriptionally.TheadditionalacetylationofH4K16definesasecondstatecharacterisedbyapproximatelytwofold elevatedJIL-1levels,whichisparticularlyprominentonthedosage-compensatedmaleXchromosome.Phosphorylationofthe histoneH3N-terminusbyJIL-1invitroiscompatiblewithothertailmodifications.Invivo,phosphorylationofH3atserine10, togetherwithacetylationatlysine14,createsacompositehistonemarkthatisenrichedatJIL-1bindingregions.Itsdepletion byRNAinterferenceleadstoamodest,butsignificant,decreaseoftranscriptionfromthemaleXchromosome.Collectively, theresultssuggestthatJIL-1participatesinacomplexhistonemodificationnetworkthatcharacterisesactive,decondensed chromatin.WehypothesisethatonespecificroleofJIL-1maybetoreinforce,ratherthantoestablish,thestatusofactive chromatinthroughthephosphorylationofhistoneH3atserine10. Citation:RegnardC,StraubT,MitterwegerA,DahlsveenIK,FabianV,etal.(2011)GlobalAnalysisoftheRelationshipbetweenJIL-1

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