Growth hormone regulation of insulin-like growth factor-I gene expression may be mediated by multiple distal signal transducer and activator of transcription 5 binding sites

dc.contributor.authorEleswarapu, Satyanarayanaen
dc.contributor.authorGu, Zhiliangen
dc.contributor.authorJiang, Honglinen
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.date.accessed2014-07-07en
dc.date.accessioned2014-07-08T13:02:15Zen
dc.date.available2014-07-08T13:02:15Zen
dc.date.issued2008-05en
dc.description.abstractThe transcription factor signal transducer and activator of transcription (STAT)-5 mediates GH stimulation of IGF-I gene expression in the liver. Previous studies suggested that STAT5 might exert this effect by binding to an IGF-I intron 2 region and a distal 5' -flanking region each containing two STAT5 binding sites. Here we report the identification of three additional chromosomal regions containing a total of five putative STAT5 binding sites that may mediate GH-induced STAT5 activation of IGF-I gene expression in the mouse liver. By comparing an 170-kb mouse genomic DNA containing the IGF-I gene with the corresponding human sequence, we identified 19 putative STAT5 binding sites that bear the consensus sequence of STAT5 binding site and are conserved across the two species. Chromatin immunoprecipitation assays indicated that five chromosomal regions containing a total of nine of the 19 putative STAT5 binding sites were bound by STAT5 in the mouse liver in response to GH administration and that these bindings preceded or coincided with GH-increased IGF-I gene transcription. Two of the five chromosomal regions correspond to those previously identified in other species, and the three new chromosomal regions that contain a total of five putative STAT5 binding sites are IGF-I intron 3 regions located at least 26 kb from the transcription start site. Gelshift assays confirmed the binding of the five new putative STAT5 binding sites as well as three of the four previously identified STAT5 binding sites to GH-activated STAT5 from the mouse liver. Cotransfection analyses indicated that, although each of the five chromosomal regions was able to mediate STAT5 activation of reporter gene expression, together they mediated greater STAT5 activation of reporter gene expression in response to GH. Overall, these results suggest that GH-induced STAT5 activation of IGF-I gene expression in the mouse liver might be collectively mediated by at least eight STAT5 binding sites located located in distal intronic and 5' -flanking regions of the IGF-I gene.en
dc.format.mimetypeapplication/pdfen
dc.identifier.citationSatyanaryana Eleswarapu, Zhiliang Gu, and Honglin Jiang. "Growth Hormone Regulation of Insulin-Like Growth Factor-I Gene Expression May Be Mediated by Multiple Distal Signal Transducer and Activator of Transcription 5 Binding Sites," Endocrinology 2008 149:5, 2230-2240. DOI: http://dx.doi.org/10.1210/en.2007-1344en
dc.identifier.doihttps://doi.org/10.1210/en.2007-1344en
dc.identifier.issn0013-7227en
dc.identifier.urihttp://hdl.handle.net/10919/49387en
dc.identifier.urlhttp://press.endocrine.org/doi/abs/10.1210/en.2007-1344en
dc.language.isoenen
dc.publisherEndocrine Societyen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectacid protein interactionsen
dc.subjectcomparative genomicsen
dc.subjectrapid activationen
dc.subjectmouse-liveren
dc.subjectdwarf miceen
dc.subjectstat5ben
dc.subjectreceptoren
dc.subjectpromoteren
dc.subjectmechanismsen
dc.subjectmutationen
dc.subjectendocrinology & metabolismen
dc.titleGrowth hormone regulation of insulin-like growth factor-I gene expression may be mediated by multiple distal signal transducer and activator of transcription 5 binding sitesen
dc.title.serialEndocrinologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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