Elevated IKKα Accelerates the Differentiation of Human Neuronal Progenitor Cells and Induces MeCP2-Dependent BDNF Expression 英文参考文献.docVIP

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Elevated IKKα Accelerates the Differentiation of Human Neuronal Progenitor Cells and Induces MeCP2-Dependent BDNF Expression 英文参考文献.doc

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Elevated IKKα Accelerates the Differentiation of Human Neuronal Progenitor Cells and Induces MeCP2-Dependent BDNF Expression 英文参考文献

ElevatedIKKaAcceleratestheDifferentiationofHuman NeuronalProgenitorCellsandInducesMeCP2- DependentBDNFExpression AliKhoshnan*,PaulH.Patterson BiologyDivision216-76,CaliforniaInstituteofTechnology,Pasadena,California,UnitedStatesofAmerica Abstract TheIkBkinasea(IKKa)isimplicatedinthedifferentiationofepithelialandimmunecells.WeexaminedwhetherIKKaalso plays a role in the differentiation and maturation of embryonic human neuronal progenitor cells (NPCs). We find that expressionofanextracopyofIKKa(IKKa+)blocksself-renewalandacceleratesthedifferentiationofNPCs.Thiscoincides withreducedexpressionoftheRepressorElementSilencingTranscriptionFactor/Neuron-RestrictiveSilencingFactor(REST/ NRSF),whichisaprominentinhibitorofneurogenesis,andsubsequentinductionofthepro-differentiationnon-codingRNA, miR-124a. However, the effects of IKKa on REST/NRSF and miR-124a expression are likely to be indirect. IKKa+ neurons display extensive neurite outgrowth andaccumulate protein markers of neuronal maturation such as SCG10/stathmin-2, postsynapticdensity95(PSD95),syntaxin,andmethyl-CpGbindingprotein2(MeCP2).Interestingly,IKKaassociateswith MeCP2 in the nuclei of human neurons and can phosphorylate MeCP2 in vitro. Using chromatin immunoprecipitation assays,wefindthatIKKaisrecruitedtotheexon-IVbrain-derived neurotrophicfactor (BDNF)promoter,which isawell- characterized target of MeCP2 activity. Moreover, IKKa induces the transcription of BDNF and knockdown expression of MeCP2interfereswiththisevent.ThesestudieshighlightaroleforIKKainacceleratingthedifferentiationofhumanNPCs andidentifyIKKaasapotentialregulatorofMeCP2functionandBDNFexpression. Citation:KhoshnanA,PattersonPH(2012)ElevatedIKKaAcceleratestheDifferentiationofHumanNeuronalProgenitorCellsandInducesMeCP2-Dependent BDNFExpression.PLoSONE7(7):e41794.doi:10.1371/journal.pone.0041794 Editor:NicolettaLandsberger,UniversityofInsubria,Italy ReceivedMarch22,2012;AcceptedJune25,2012;PublishedJuly27,2012 Copyright:?2012Khoshnan,Patter