Microarray Analysis Uncovers a Role for Tip60 in Nervous System Function and General Metabolism 英文参考文献.docVIP

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Microarray Analysis Uncovers a Role for Tip60 in Nervous System Function and General Metabolism 英文参考文献.doc

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Microarray Analysis Uncovers a Role for Tip60 in Nervous System Function and General Metabolism 英文参考文献

MicroarrayAnalysisUncoversaRoleforTip60inNervous SystemFunctionandGeneralMetabolism MeridithLorbeck,KeerthyPirooznia.,JessicaSarthi.,XianminZhu¤,FeliceElefant* DepartmentofBiology,DrexelUniversity,Philadelphia,Pennsylvania,UnitedStatesofAmerica Abstract Background:Tip60isakeyhistoneacetyltransferase(HAT)enzymethatplaysacentralroleindiversebiologicalprocesses critical for general cell function; however, the chromatin-mediated cell-type specific developmental pathways that are dependentexclusivelyupontheHATactivityofTip60remaintobeexplored. MethodsandFindings:Here,weinvestigatetheroleofTip60HATactivityintranscriptionalcontrolduringmulticellular development in vivo by examining genome-wide changes in gene expression in a Drosophila model system specifically depletedforendogenousdTip60HATfunction. Conclusions:WeshowthataminoacidresidueE431inthecatalyticHATdomainofdTip60iscriticalfortheacetylationof endogenous histone H4 in our fly model in vivo, and demonstrate that dTip60 HAT activity is essential for multicellular development. Moreover, our results uncover a novel role for Tip60 HAT activity in controlling neuronal specific gene expression profiles essential for nervous system function as well as a central regulatory role for Tip60 HAT function in generalmetabolism. Citation: Lorbeck M, Pirooznia K, Sarthi J, Zhu X, Elefant F (2011) Microarray Analysis Uncovers a Role for Tip60 in Nervous System Function and General Metabolism.PLoSONE6(4):e18412.doi:10.1371/journal.pone.0018412 Editor:JosephNajbauer,CityofHopeNationalMedicalCenterandBeckmanResearchInstitute,UnitedStatesofAmerica ReceivedOctober27,2010;AcceptedMarch7,2011;PublishedApril11,2011 Copyright: ? 2011 Lorbeck 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:ThisworkwasfundedbyaNationalInstitutesofHealthgrant()1R01HD057939to