Psip1Ledgf p52 Binds Methylated Histone H3K36 and Splicing Factors and Contributes to the Regulation of Alternative Splicing 英文参考文献.docVIP

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Psip1Ledgf p52 Binds Methylated Histone H3K36 and Splicing Factors and Contributes to the Regulation of Alternative Splicing 英文参考文献.doc

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Psip1Ledgf p52 Binds Methylated Histone H3K36 and Splicing Factors and Contributes to the Regulation of Alternative Splicing 英文参考文献

Psip1/Ledgfp52BindsMethylatedHistoneH3K36and SplicingFactorsandContributestotheRegulationof AlternativeSplicing MadapuraM.Pradeepa1,HeidiG.Sutherland1,JernejUle2,GraemeR.Grimes1,WendyA.Bickmore1* 1MRCHumanGeneticsUnit,MRCInstituteofGeneticsandMolecularMedicine,UniversityofEdinburgh,Edinburgh,UnitedKingdom, 2MRCLaboratoryofMolecular Biology,Cambridge,UnitedKingdom Abstract Increasingevidencesuggeststhatchromatinmodificationshaveimportantrolesinmodulatingconstitutiveoralternative splicing. Here we demonstrate that the PWWP domain of the chromatin-associated protein Psip1/Ledgf can specifically recognizetri-methylatedH3K36andthat,likethishistonemodification,thePsip1short(p52)isoformisenrichedatactive genes. We show that the p52, but not the long (p75), isoform of Psip1 co-localizes and interacts with Srsf1 and other proteins involved in mRNA processing. The level of H3K36me3 associated Srsf1 is reduced in Psip1 mutant cells and alternative splicing of specific genes is affected. Moreover, we show altered Srsf1 distribution around the alternatively spliced exons ofthese genesin Psip1null cells. Wepropose that Psip1/p52, through itsbinding toboth chromatin and splicingfactors,mightacttomodulatesplicing. Citation: Pradeepa MM, Sutherland HG, Ule J, Grimes GR, Bickmore WA (2012) Psip1/Ledgf p52 Binds Methylated Histone H3K36 and Splicing Factors and ContributestotheRegulationofAlternativeSplicing.PLoSGenet8(5):e1002717.doi:10.1371/journal.pgen.1002717 Editor:WolfReik,TheBabrahamInstitute,UnitedKingdom ReceivedDecember29,2011;AcceptedApril2,2012;PublishedMay17,2012 Copyright: ? 2012 Pradeepa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbyaprojectgrantfromtheWellcomeTrust(grantno.WT085767)andbyaunitprogrammegrantfromtheMedicalResearch Council,UK.Thefundersh