Silencing and Nuclear Repositioning of the λ5 Gene Locus at the Pre-B Cell Stage Requires Aiolos and OBF-1 英文参考文献.docVIP

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Silencing and Nuclear Repositioning of the λ5 Gene Locus at the Pre-B Cell Stage Requires Aiolos and OBF-1 英文参考文献.doc

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Silencing and Nuclear Repositioning of the λ5 Gene Locus at the Pre-B Cell Stage Requires Aiolos and OBF-1 英文参考文献

SilencingandNuclearRepositioningofthel 5Gene LocusatthePre-BCellStageRequiresAiolosandOBF-1 AlexanderKarnowski1,2,ChunCao1,GabrieleMatthias1,SebastianCarotta2,LynnM.Corcoran2 ,Inga-Lill Martensson3,JaneA.Skok4,5,PatrickMatthias1* 1FriedrichMiescherInstituteforBiomedicalResearch,NovartisResearchFoundation,Basel,Switzerland,2TheWalterandElizaHallInstituteofMedicalResearch,Parkville, Victoria, Australia, 3Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Cambridge, United Kingdom, 4Department of Immunologyand MolecularPathology,UniversityCollegeLondon,London,UnitedKingdom,5NewYorkUniversitySchoolofMedicine,NewYork,NewYork,UnitedStatesofAmerica Abstract ThechromatinregulatorAiolosandthetranscriptionalcoactivatorOBF-1havebeenimplicatedinregulatingaspectsofB cellmaturationandactivation.MicelackingeitherofthesefactorshavealargelynormalearlyBcelldevelopment.However, whenbothfactorsareeliminatedsimultaneouslyablockisuncoveredatthetransitionbetweenpre-BandimmatureBcells, indicatingthattheseproteinsexertacriticalfunctionindevelopingBlymphocytes.InmicedeficientforAiolosandOBF-1, the numbers of immature B cells are reduced, small pre-BII cells are increased and a significant impairment in immunoglobulinlightchainDNArearrangementisobserved.Weidentifiedgeneswhoseexpressionisderegulatedinthe pre-Bcellcompartmentofthesemice.Inparticular,wefoundthatcomponentsofthepre-BCR,suchasthesurrogatelight chain genes l5 and VpreB, fail to be efficiently silenced in double-mutant mice. Strikingly, developmentally regulated nuclearrepositioningofthel5geneisimpairedinpre-BcellslackingOBF-1andAiolos.Thesestudiesuncoveranovelrole forOBF-1andAiolosincontrollingthetranscriptionandnuclearorganizationofgenesinvolvedinpre-BCRfunction. Citation:KarnowskiA,CaoC,MatthiasG,CarottaS,CorcoranLM,etal.(2008)SilencingandNuclearRepositioningofthel5GeneLocusatthePre-BCellStage RequiresAiolosandOBF-1.PLoSONE3(10):e3568.doi:10.1371/journal.pone.0003568 Editor:SebastianD.Fugmann,NationalIns