SFRS7-Mediated Splicing of Tau Exon 10 Is Directly Regulated by STOX1A in Glial Cells 英文参考文献.docVIP

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SFRS7-Mediated Splicing of Tau Exon 10 Is Directly Regulated by STOX1A in Glial Cells 英文参考文献.doc

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SFRS7-Mediated Splicing of Tau Exon 10 Is Directly Regulated by STOX1A in Glial Cells 英文参考文献

SFRS7-MediatedSplicingofTauExon10IsDirectly RegulatedbySTOX1AinGlialCells DaanvanAbel1,DennisR.Ho¨lzel2,ShushantJain2,FionaM.F.Lun3,YamaW.L.Zheng3,EricZ.Chen3, HaoSun3,RossaW.K.Chiu3,Y.M.DennisLo3,MarievanDijk1,CeesB.M.Oudejans1* 1Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands, 2Department of Clinical Genetics, Section Medical Genomics, VU UniversityMedicalCenter,Amsterdam,TheNetherlands,3DepartmentofChemicalPathology,PrinceofWalesHospital,Shatin,NewTerritories,HongKongSAR,China Abstract Background: In this study, we performed a genome-wide search for effector genes bound by STOX1A, a winged helix transcription factor recently demonstrated to be involved in late onset Alzheimer’s disease and affecting the amyloid processingpathway. Methodology/PrincipalFindings:Ourresultsshowthatoutof218genesboundbySTOX1Aasidentifiedbychromatin- immunoprecipitationfollowedbysequencing(ChIP-Seq),theserine/arginine-richsplicingfactor7(SFRS7)wasfoundtobe induced,bothatthemRNAandproteinlevels,bySTOX1Aafterstabletransfectioninglialcells.TheincreaseinSFRS7was followedbyanincreaseinthe4R/3Rratiosofthemicrotubule-associatedproteintau(MAPT)bydifferentialexon10splicing. Secondly, STOX1A also induced expression of total tau both at the mRNA and protein levels. Upregulation of total tau expression(SFRS7-independent)andtauexon10splicing(SFRS7-dependent),asshowninthisstudytobebothaffectedby STOX1A,isknowntohaveimplicationsinneurodegeneration. Conclusions:OurdatafurthersupportsthefunctionalimportanceandcentralroleofSTOX1Ainneurodegeneration. Citation: vanAbelD,Ho¨lzelDR,JainS,LunFMF,ZhengYWL,etal.(2011)SFRS7-MediatedSplicingofTauExon10IsDirectlyRegulatedbySTOX1AinGlial Cells.PLoSONE6(7):e21994.doi:10.1371/journal.pone.0021994 Editor:AndreaC.LeBlanc,McGillUniversity,Canada ReceivedMarch19,2011;AcceptedJune10,2011;PublishedJuly6,2011 Copyright: ? 2011 van Abel et al. This is an open-access article distributed under the terms of the Creative Commons Attri