Chicken ovalbumin upstream promoter-transcription factor II regulates nuclear receptor, myogenic, and metabolic gene expression in skeletal muscle cells
| Autor: | Lauren A. Murray, Shu-Ching Mary Wang, Natalie A. Eriksson, Lisa M. Crowther, Stephen Myers, George E.O. Muscat |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Transcriptional Activation Physiology Chicken ovalbumin upstream promoter-transcription factor Muscle Fibers Skeletal Biology Muscle Development Cell Line COUP Transcription Factor II Mice Gene expression Genetics medicine Animals Humans RNA Messenger Muscle Skeletal Promoter Regions Genetic Oligonucleotide Array Sequence Analysis Messenger RNA Muscle Cells Glucose Transporter Type 4 Myogenesis Skeletal muscle Gene Expression Regulation Developmental Molecular biology Rats Ovalbumin medicine.anatomical_structure Nuclear receptor biology.protein C2C12 Protein Binding |
| Zdroj: | Physiological genomics. 43(4) |
| ISSN: | 1531-2267 |
| Popis: | We demonstrate that chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) mRNA is more abundantly expressed (than COUP-TFI mRNA) in skeletal muscle C2C12 cells and in (type I and II) skeletal muscle tissue from C57BL/10 mice. Consequently, we have utilized the ABI TaqMan Low Density Array (TLDA) platform to analyze gene expression changes specifically attributable to ectopic COUP-TFII (relative to vector only) expression in muscle cells. Utilizing a TLDA-based platform and 5 internal controls, we analyze the entire NR superfamily, 96 critical metabolic genes, and 48 important myogenic regulatory genes on the TLDA platform utilizing 5 internal controls. The low density arrays were analyzed by rigorous statistical analysis (with Genorm normalization, Bioconductor R, and the Empirical Bayes statistic) using the (integromics) statminer software. In addition, we validated the differentially expressed patho-physiologically relevant gene (identified on the TLDA platform) glucose transporter type 4 (Glut4). We demonstrated that COUP-TFII expression increased the steady state levels of Glut4 mRNA and protein, while ectopic expression of truncated COUP-TFII lacking helix 12 (COUP-TFΔH12) reduced Glut4 mRNA expression in C2C12 cells. Moreover, COUP-TFII expression trans-activated the Glut4 promoter (−997/+3), and ChIP analysis identified selective recruitment of COUP-TFII to a region encompassing a highly conserved SP1 binding site (in mouse, rat, and human) at nt positions −131/−118. Mutation of the SpI site ablated COUP-TFII mediated trans-activation of the Glut4 promoter. In conclusion, this study demonstrates that in skeletal muscle cells, COUP-TFII regulates several nuclear hormone receptors, and critical metabolic and muscle specific genes. |
| Databáze: | OpenAIRE |
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