c-Myc Is Required for the ChREBP-Dependent Activation of Glucose-Responsive Genes
| العنوان: | c-Myc Is Required for the ChREBP-Dependent Activation of Glucose-Responsive Genes |
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| المؤلفون: | Edward V. Prochownik, Robert M. O'Doherty, Mallikarjurna R. Metukuri, Pili Zhang, Donald K. Scott, Sharell M. Bindom |
| المصدر: | Molecular Endocrinology. 24:1274-1286 |
| بيانات النشر: | The Endocrine Society, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Transcriptional Activation, Transcription, Genetic, Molecular Sequence Data, Pyruvate Kinase, RNA polymerase II, Article, Proto-Oncogene Proteins c-myc, Islets of Langerhans, Endocrinology, Transcription (biology), Cell Line, Tumor, Gene expression, Animals, Humans, Promoter Regions, Genetic, Carbohydrate-responsive element-binding protein, Molecular Biology, Transcription factor, Binding Sites, Base Sequence, Models, Genetic, biology, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, General Medicine, Molecular biology, Rats, Thiazoles, Hepatocyte nuclear factors, Glucose, Liver, Organ Specificity, biology.protein, Chromatin immunoprecipitation, Pyruvate kinase, Protein Binding, Transcription Factors |
| الوصف: | Glucose regulates programs of gene expression that orchestrate changes in cellular phenotype in several metabolically active tissues. Carbohydrate response element-binding protein (ChREBP) and its binding partner, Mlx, mediate glucose-regulated gene expression by binding to carbohydrate response elements on target genes, such as the prototypical glucose-responsive gene, liver-type pyruvate kinase (Pklr). c-Myc is also required for the glucose response of the Pklr gene, although the relationship between c-Myc and ChREBP has not been defined. Here we describe the molecular events of the glucose-mediated activation of Pklr and determine the effects of decreasing the activity or abundance of c-Myc on this process. Time-course chromatin immunoprecipitation revealed a set of transcription factors [hepatocyte nuclear factor (HNF)1α, HNF4α, and RNA polymerase II (Pol II)] constitutively resident on the Pklr promoter, with a relative enrichment of acetylated histones 3 and 4 in the same region of the gene. Glucose did not affect HNF1α binding or the acetylation of histones H3 or H4. By contrast, glucose promoted the recruitment of ChREBP and c-Myc and increased the occupancy of HNF4α and RNA Pol II, which were coincident with the glucose-mediated increase in transcription as determined by a nuclear run-on assay. Depletion of c-Myc activity using a small molecule inhibitor (10058-F4/1RH) abolished the glucose-mediated recruitment of HNF4α, ChREBP, and RNA Pol II, without affecting basal gene expression, histone acetylation, and HNF1α or basal HNF4α occupancy. The activation and recruitment of ChREBP to several glucose-responsive genes were blocked by 1RH, indicating a general necessity for c-Myc in this process. |
| تدمد: | 1944-9917 0888-8809 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6f36ba00bfcadcbebe24058850322a76Test https://doi.org/10.1210/me.2009-0437Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....6f36ba00bfcadcbebe24058850322a76 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19449917 08888809 |
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