HDAC Activity Is Required during Xenopus Tail Regeneration 英文参考文献.docVIP

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HDAC Activity Is Required during Xenopus Tail Regeneration 英文参考文献.doc

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HDAC Activity Is Required during Xenopus Tail Regeneration 英文参考文献

HDACActivityIsRequiredduringXenopusTail Regeneration Ai-SunTseng1.,Ka′tiaCarneiro2.,JoanM.Lemire1,MichaelLevin1* 1Department of Developmental Biology, Center for Regenerative and Developmental Biology, Tufts University, Medford, Massachusetts, United States of America, 2DepartmentofHistologyandEmbryology,InstituteofBiomedicalSciences,FederalUniversityofRiodeJaneiro,RiodeJaneiro,Brazil Abstract The ability to fully restore damaged or lost organs is present in only a subset of animals. The Xenopus tadpole tail is a complex appendage, containing epidermis, muscle, nerves, spinal cord, and vasculature, which regenerates after amputation. Understanding the mechanisms of tail regeneration may lead to new insights to promote biomedical regenerationinnon-regenerativetissues.Althoughchromatinremodelingisknowntobecriticalforstemcellpluripotency, its role in complex organ regeneration in vivo remains largely uncharacterized. Here we show that histone deacetylase (HDAC) activity is required for the early stages of tail regeneration. HDAC1 is expressed during the 1st two days of regeneration. Pharmacological blockade of HDACs using Trichostatin A (TSA) increased histone acetylation levels in the amputated tail. Furthermore, treatment with TSA or another HDAC inhibitor, valproic acid, specifically inhibited regeneration.Over-expressionofwild-typeMad3,atranscriptionalrepressorknowntoassociateinacomplexwithHDACs viaSin3,inhibitedregeneration.Similarly,expressionofaMad3mutantlackingtheSin3-interactingdomainthatisrequired forHDACbindingalsoblocksregeneration,suggestingthatHDACandMad3mayacttogethertoregulateregeneration. InhibitionofHDACfunctionresultedinaberrantexpressionofNotch1andBMP2,twogenesknowntoberequiredfortail regeneration.OurresultsidentifyanovelearlyroleforHDACinappendageregenerationandsuggestthatmodulationof histoneacetylationisimportantinregenerativerepairofcomplexappendages. Citation:TsengA-S,CarneiroK,LemireJM,LevinM(2011)HDACActivityIsRequiredduringXenopusTailRege