Dynamics of Passive and Active Particles in the Cell Nucleus 英文参考文献.docVIP

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Dynamics of Passive and Active Particles in the Cell Nucleus 英文参考文献.doc

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Dynamics of Passive and Active Particles in the Cell Nucleus 英文参考文献

DynamicsofPassiveandActiveParticlesintheCell Nucleus FerozM.Hameed1,MadanRao2,3,G.V.Shivashankar1* 1MechanobiologyInstitute,andDepartmentofBiologicalSciences,NationalUniversityofSingapore,Singapore,2NationalCentreforBiologicalSciences,TataInstituteof FundamentalResearch,Bangalore,India,3RamanResearchInstitute,Bangalore,India Abstract Inspiteofbeingembeddedinadensemeshworkofnuclearchromatin,genelociandlargenuclearcomponentsarehighly dynamicat370C.Tounderstandthisapparentunfetteredmovementinanoverdenseenvironment,westudythedynamics 0 ofapassivemicronsizebeadinlivecellnucleiattwodifferenttemperatures(25and37C)withandwithoutexternalforce. Intheabsenceofaforce,thebeadsarecagedoverlargetimescales.Onapplicationofathresholduniaxialforce(about102 pN),thepassivebeadsappeartohopbetweencages;thislargescalemovementisabsentuponATP-depletion,inhibitionof chromatinremodelingenzymesandRNAioflaminB1proteins.Ourresultssuggestthatthenucleusbehaveslikeanactive solidwithafiniteyieldstresswhenprobedatamicronscale.Spatialanalysisofhistonefluorescenceanisotropy(ameasure oflocalchromatincompaction,definedasthevolumefractionoftightlyboundchromatin)showsthatthebeadmovement correlateswithregionsoflowchromatincompaction.Thissuggeststhatthephysicalmechanismoftheobservedyieldingis theactiveopeningoffree-volumeinthenuclearsolidviachromatinremodeling.Enrichedtranscriptionsitesat250 Calso showcagingintheabsenceoftheappliedforceanddirectedmovementbeyondayieldstress,instrikingcontrastwiththe large scale movement of transcription loci at 370C in the absence of a force. This suggests that at physiological temperatures,thelocibehaveasactiveparticleswhichremodelthenuclearmeshandreducethelocalyieldstress. Citation: Hameed FM, Rao M, Shivashankar GV (2012) Dynamics of Passive and Active Particles in the Cell Nucleus. PLoS ONE 7(10): e45843. doi:10.1371/ journal.pone.0045843 Editor:AndreVanWijnen,UniversityofMassachusettsMedical,UnitedStatesofAmerica ReceivedMarch22,2012;AcceptedAugust24,2012;PublishedOctob