Paired Hormone Response Elements Predict Caveolin-1 as a Glucocorticoid Target Gene 英文参考文献.docVIP

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Paired Hormone Response Elements Predict Caveolin-1 as a Glucocorticoid Target Gene 英文参考文献.doc

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PairedHormoneResponseElementsPredictCaveolin-1 asaGlucocorticoidTargetGene MarinusF.vanBatenburg1,2.,HualingLi4,5.,J.AnneliesPolman3,ServaneLachize3,NicoleA.Datson3, HarmenJ.Bussemaker2,6,OnnoC.Meijer3* 1Bioinformatics Laboratory, Academic Medical Center, Amsterdam, The Netherlands, 2Department of Biological Sciences, Columbia University, New York, New York, United States of America, 3Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research and Leiden University Medical Center, Amsterdam, The Netherlands, 4Department of Biochemistry and Molecular Biology, Life Science College of Nanjing Agriculture University, Nanjing, People’s Republic of China, 5DepartmentofBiochemistryandMolecularBiology,MedicalCollegeofYangzhouUniversity,Yangzhou,People’sRepublicofChina,6CenterforComputationalBiology andBioinformatics,ColumbiaUniversityMedicalCenter,NewYork,NewYork,UnitedStatesofAmerica Abstract Glucocorticoids act in part via glucocortocoid receptor binding to hormone response elements (HREs), but their direct targetgenesinvivoarestilllargelyunknown.WedevelopedthecriterionthatgenomicoccurrenceofpairedHREsatan inter-HRE distance less than 200bp predicts hormone responsiveness, based on synergy of multiple HREs, and HRE informationfromknowntargetgenes.Thiscriterionpredictsasubstantialnumberofnovelresponsivegenes,whenapplied togenomicregions10kbupstreamofgenes.Multiple-tissueinsituhybridizationshowedthatmRNAexpressionof6outof 10selectedgeneswasinducedinatissue-specificmannerinmicetreatedwithasingledoseofcorticosterone,withthe spleen being the most responsive organ. Caveolin-1 was strongly responsive in several organs, and the HRE pair in its upstream region showed increased occupancy by glucocorticoid receptor in response to corticosterone. Our approach allowedfordiscoveryofnoveltissuespecificglucocorticoidtargetgenes,whichmayexemplifyresponsesunderlyingthe permissiveactionsofglucocorticoids. Citation: vanBatenburg MF, LiH, PolmanJA, Lachize S,Datson NA,et al.