Selective Histonedeacetylase Inhibitor M344 Intervenes in HIV-1 Latency through Increasing Histone Acetylation and Activation of NF-kappaB 英文参考文献.docVIP

Selective Histonedeacetylase Inhibitor M344 Intervenes in HIV-1 Latency through Increasing Histone Acetylation and Activation of NF-kappaB 英文参考文献.doc

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Selective Histonedeacetylase Inhibitor M344 Intervenes in HIV-1 Latency through Increasing Histone Acetylation and Activation of NF-kappaB 英文参考文献

SelectiveHistonedeacetylaseInhibitorM344Intervenes inHIV-1LatencythroughIncreasingHistoneAcetylation andActivationofNF-kappaB HaoYing.,YuhaoZhang.,XinZhou.,XiyingQu,PengfeiWang,SijieLiu,DaruLu,HuanzhangZhu* StateKeyLaboratoryofGeneticEngineering,InstituteofGenetics,SchoolofLifeSciences,FudanUniversity,Shanghai,China Abstract Background: Histone deacetylase (HDAC) inhibitors present an exciting new approach to activate HIV production from latentlyinfectedcellstopotentiallyenhanceeliminationofthesecellsandachieveacure.M344,anovelHDACinhibitor, showsrobustactivityinavarietyofcancercellsandrelativelylowtoxicitycomparedtotrichostatinA(TSA).However,littleis knownabouttheeffectsandactionmechanismofM344ininducingHIVexpressioninlatentlyinfectedcells. Methodology/Principal Findings: Using the Jurkat T cell model of HIV latency, we demonstrate that M344 effectively reactivatesHIV-1geneexpressioninlatentlyinfectedcells.Moreover,M344-mediatedactivationofthelatentHIVLTRcanbe stronglyinhibitedbyaNF-kBinhibitoraspirin.WefurthershowthatM344actsbyincreasingtheacetylationofhistoneH3 andhistoneH4atthenucleosome1(nuc-1)siteoftheHIV-1longterminalrepeat(LTR)andbyinducingNF-kBp65nuclear translocationanddirectRelADNAbindingatthenuc-1regionoftheHIV-1LTR.WealsofoundthatM344synergizedwith prostratintoactivatetheHIV-1LTRpromoterinlatentlyinfectedcells. Conclusions/Significance:TheseresultssuggestthepotentialofM344inanti-latencytherapiesandanimportantrolefor histonemodificationsandNF-kBtranscriptionfactorsinregulatingHIV-1LTRgeneexpression. Citation: Ying H, Zhang Y, Zhou X, Qu X, Wang P, et al. (2012) Selective Histonedeacetylase Inhibitor M344 Intervenes in HIV-1 Latency through Increasing HistoneAcetylationandActivationofNF-kappaB.PLoSONE7(11):e48832.doi:10.1371/journal.pone.0048832 Editor:FatahKashanchi,GeorgeMasonUniversity,UnitedStatesofAmerica ReceivedMarch21,2012;AcceptedOctober5,2012;PublishedNovember15,2012 Copyright:?2012Yingetal.Thisisanopen-accessarticledistributedunderthetermsoft

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