Regulation of expression of citrate synthase by the retinoic acid receptor-related orphan receptor α (RORα).
The retinoic acid receptor-related orphan receptor α (RORα) is a member of the nuclear receptor superfamily of transcription factors that plays an important role in regulation of the circadian rhythm and metabolism. Mice lacking a functional RORα display a range of metabolic abnormalities including...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3317774?pdf=render |
| _version_ | 1818859175565852672 |
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| author | Christine Crumbley Yongjun Wang Subhashis Banerjee Thomas P Burris |
| author_facet | Christine Crumbley Yongjun Wang Subhashis Banerjee Thomas P Burris |
| author_sort | Christine Crumbley |
| collection | DOAJ |
| description | The retinoic acid receptor-related orphan receptor α (RORα) is a member of the nuclear receptor superfamily of transcription factors that plays an important role in regulation of the circadian rhythm and metabolism. Mice lacking a functional RORα display a range of metabolic abnormalities including decreased serum cholesterol and plasma triglycerides. Citrate synthase (CS) is a key enzyme of the citric acid cycle that provides energy for cellular function. Additionally, CS plays a critical role in providing citrate derived acetyl-CoA for lipogenesis and cholesterologenesis. Here, we identified a functional RORα response element (RORE) in the promoter of the CS gene. ChIP analysis demonstrates RORα occupancy of the CS promoter and a putative RORE binds to RORα effectively in an electrophoretic mobility shift assay and confers RORα responsiveness to a reporter gene in a cotransfection assay. We also observed a decrease in CS gene expression and CS enzymatic activity in the staggerer mouse, which has a mutation of in the Rora gene resulting in nonfunctional RORα protein. Furthermore, we found that SR1001 a RORα inverse agonist eliminated the circadian pattern of expression of CS mRNA in mice. These data suggest that CS is a direct RORα target gene and one mechanism by which RORα regulates lipid metabolism is via regulation of CS expression. |
| first_indexed | 2024-12-19T09:08:00Z |
| format | Article |
| id | doaj.art-b193c114b6e04ce785a465c2caeae41c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T09:08:00Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b193c114b6e04ce785a465c2caeae41c2022-12-21T20:28:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3380410.1371/journal.pone.0033804Regulation of expression of citrate synthase by the retinoic acid receptor-related orphan receptor α (RORα).Christine CrumbleyYongjun WangSubhashis BanerjeeThomas P BurrisThe retinoic acid receptor-related orphan receptor α (RORα) is a member of the nuclear receptor superfamily of transcription factors that plays an important role in regulation of the circadian rhythm and metabolism. Mice lacking a functional RORα display a range of metabolic abnormalities including decreased serum cholesterol and plasma triglycerides. Citrate synthase (CS) is a key enzyme of the citric acid cycle that provides energy for cellular function. Additionally, CS plays a critical role in providing citrate derived acetyl-CoA for lipogenesis and cholesterologenesis. Here, we identified a functional RORα response element (RORE) in the promoter of the CS gene. ChIP analysis demonstrates RORα occupancy of the CS promoter and a putative RORE binds to RORα effectively in an electrophoretic mobility shift assay and confers RORα responsiveness to a reporter gene in a cotransfection assay. We also observed a decrease in CS gene expression and CS enzymatic activity in the staggerer mouse, which has a mutation of in the Rora gene resulting in nonfunctional RORα protein. Furthermore, we found that SR1001 a RORα inverse agonist eliminated the circadian pattern of expression of CS mRNA in mice. These data suggest that CS is a direct RORα target gene and one mechanism by which RORα regulates lipid metabolism is via regulation of CS expression.http://europepmc.org/articles/PMC3317774?pdf=render |
| spellingShingle | Christine Crumbley Yongjun Wang Subhashis Banerjee Thomas P Burris Regulation of expression of citrate synthase by the retinoic acid receptor-related orphan receptor α (RORα). PLoS ONE |
| title | Regulation of expression of citrate synthase by the retinoic acid receptor-related orphan receptor α (RORα). |
| title_full | Regulation of expression of citrate synthase by the retinoic acid receptor-related orphan receptor α (RORα). |
| title_fullStr | Regulation of expression of citrate synthase by the retinoic acid receptor-related orphan receptor α (RORα). |
| title_full_unstemmed | Regulation of expression of citrate synthase by the retinoic acid receptor-related orphan receptor α (RORα). |
| title_short | Regulation of expression of citrate synthase by the retinoic acid receptor-related orphan receptor α (RORα). |
| title_sort | regulation of expression of citrate synthase by the retinoic acid receptor related orphan receptor α rorα |
| url | http://europepmc.org/articles/PMC3317774?pdf=render |
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