Modulation of Thyroid Hormone-Dependent Gene Expression in Xenopus laevis by INhibitor of Growth (ING) Proteins 英文参考文献.docVIP

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Modulation of Thyroid Hormone-Dependent Gene Expression in Xenopus laevis by INhibitor of Growth (ING) Proteins 英文参考文献.doc

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Modulation of Thyroid Hormone-Dependent Gene Expression in Xenopus laevis by INhibitor of Growth (ING) Proteins 英文参考文献

ModulationofThyroidHormone-DependentGene ExpressioninXenopuslaevisbyINhibitorofGrowth (ING)Proteins CarenC.Helbing1*,MaryJ.Wagner1,KatherinePettem1,JillJohnston2¤,RachelA.Heimeier3 ,Nik Veldhoen1,FrankR.Jirik2,4,Yun-BoShi3,LeonW.Browder2 1DepartmentofBiochemistryMicrobiology,UniversityofVictoria,Victoria,BritishColumbia,Canada,2DepartmentofBiochemistryandMolecularBiology,Universityof Calgary,Calgary,Alberta,Canada,3SectiononMolecularMorphogenesis,LaboratoryofGeneRegulationandDevelopment,ProgramonCellRegulationandMetabolism, NationalInstituteofChildHealthandHumanDevelopment,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica,4TheMcCaigInstituteforBone andJointHealth,UniversityofCalgary,Calgary,Alberta,Canada Abstract Background:INhibitorofGrowth(ING)proteinsbelongtoalargefamilyofplanthomeodomainfinger-containingproteins important in epigenetic regulation and carcinogenesis. We have previously shown that ING1 and ING2 expression is regulatedbythyroidhormone(TH)duringmetamorphosisoftheXenopuslaevistadpole.Thepresentstudyinvestigatesthe possibilitythatINGproteinsmodulateTHaction. Methodology/PrincipalFindings:TadpolesexpressingaXenopusING2transgene(TransING2)weresignificantlysmallerthan tadpoles not expressing the transgene (TransGFP). When exposed to 10nM 3,5,39-triiodothyronine (T3 ), premetamorphic TransING2 tadpolesexhibitedagreaterreductionintail,head,andbrainareas,andaprotrusionofthelowerjawthanT3- treatedTransGFP tadpoles.Quantitativerealtimepolymerasechainreaction(QPCR)demonstratedelevatedTHreceptorb (TRb) and TH/bZIP transcript levels in TransING2 tadpole tails compared to TransGFP tadpoles while TRa mRNAs were unaffected.Incontrast,nodifferenceinTRa,TRborinsulin-likegrowthfactor(IGF2)mRNAabundancewasobservedinthe brainbetweenTransING2andTransGFPtadpoles.Allofthesetranscripts,exceptforTRamRNAinthebrain,wereinducibleby thehormoneinbothtissues.OocytetranscriptionassaysindicatedthatINGproteinsenhancedTR-dependent,T3-induced TRbgenepromoteractivity