A novel muscle DNA-binding activity in the GLUT1 promoter.
GLUT1 glucose transporters are highly expressed in proliferating and transformed cells and serum and cAMP or the transcription factor Sp1 induce GLUT1 gene transcription. Here we identified a cis element situated at -46/-37 (MG1E - muscle-specific GLUT1 element) to which muscle-specific nuclear factors bind, and the DNA-protein complexes showed electrophoretic mobility of 41 and 32 kDa. MyoD over-expression induced the generation of MG1E-protein complexes characteristic of myoblast cells. MG1E does not bind any known factors defined in databases. Mutation of the MG1E sequence impaired transcriptional activity of the GLUT1 promoter specifically in skeletal or cardiac muscle cells. The transcriptional activity of the GLUT1 promoter induced by either Sp1, cAMP or serum was markedly reduced when MG1E was inactivated. We propose that the MG1E sequence permits the binding of muscle-specific nuclear factors and a maximal transcriptional activity in muscle cells in response to Sp1, cAMP or serum.
Sánchez-Feutrie
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Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Spain.
Santalucía
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Viñals
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Brand
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Palacín
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Zorzano
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D000818:Animals; D015500:Chloramphenicol O-Acetyltransferase; D000242:Cyclic AMP / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D017570:MyoD Protein / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D020218:Response Elements; D017384:Sequence Deletion; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D004268:DNA-Binding Proteins; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D017570:MyoD Protein; D018006:Myogenic Regulatory Factors; D009687:Nuclear Proteins; C495679:Slc2a1 protein, rat; D016329:Sp1 Transcription Factor; D000242:Cyclic AMP; D015500:Chloramphenicol O-Acetyltransferase