The mechanism mediating the activation of acetyl-coenzyme A carboxylase-α gene transcription by the liver X receptor agonist T0-901317
In birds and mammals, agonists of the liver X receptor (LXR) increase the expression of enzymes that make up the fatty acid synthesis pathway. Here, we investigate the mechanism by which the synthetic LXR agonist, T0-901317, increases the transcription of the acetyl-coenzyme A carboxylase-α (ACCα) g...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2006-11-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520433814 |
| _version_ | 1818646775277289472 |
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| author | Saswata Talukdar F. Bradley Hillgartner |
| author_facet | Saswata Talukdar F. Bradley Hillgartner |
| author_sort | Saswata Talukdar |
| collection | DOAJ |
| description | In birds and mammals, agonists of the liver X receptor (LXR) increase the expression of enzymes that make up the fatty acid synthesis pathway. Here, we investigate the mechanism by which the synthetic LXR agonist, T0-901317, increases the transcription of the acetyl-coenzyme A carboxylase-α (ACCα) gene in chick embryo hepatocyte cultures. Transfection analyses demonstrate that activation of ACCα transcription by T0-901317 is mediated by a cis-acting regulatory unit (−101 to −71 bp) that is composed of a liver X receptor response element (LXRE) and a sterol-regulatory element (SRE). The SRE enhances the ability of the LXRE to activate ACCα transcription in the presence of T0-901317. Treating hepatocytes with T0-901317 increases the concentration of mature sterol-regulatory element binding protein-1 (SREBP-1) in the nucleus and the acetylation of histone H3 and histone H4 at the ACCα LXR response unit. These results indicate that T0-901317 increases hepatic ACCα transcription by directly activating LXR•retinoid X receptor (RXR) heterodimers and by increasing the activity of an accessory transcription factor (SREBP-1) that enhances ligand induced-LXR•RXR activity. |
| first_indexed | 2024-12-17T00:52:00Z |
| format | Article |
| id | doaj.art-31871c7eecb44bc3a3104df9a5d0192c |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-17T00:52:00Z |
| publishDate | 2006-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-31871c7eecb44bc3a3104df9a5d0192c2022-12-21T22:09:43ZengElsevierJournal of Lipid Research0022-22752006-11-01471124512461The mechanism mediating the activation of acetyl-coenzyme A carboxylase-α gene transcription by the liver X receptor agonist T0-901317Saswata Talukdar0F. Bradley Hillgartner1Department of Biochemistry and Molecular Pharmacology, School of Medicine, West Virginia University, Morgantown, WV 26506Department of Biochemistry and Molecular Pharmacology, School of Medicine, West Virginia University, Morgantown, WV 26506In birds and mammals, agonists of the liver X receptor (LXR) increase the expression of enzymes that make up the fatty acid synthesis pathway. Here, we investigate the mechanism by which the synthetic LXR agonist, T0-901317, increases the transcription of the acetyl-coenzyme A carboxylase-α (ACCα) gene in chick embryo hepatocyte cultures. Transfection analyses demonstrate that activation of ACCα transcription by T0-901317 is mediated by a cis-acting regulatory unit (−101 to −71 bp) that is composed of a liver X receptor response element (LXRE) and a sterol-regulatory element (SRE). The SRE enhances the ability of the LXRE to activate ACCα transcription in the presence of T0-901317. Treating hepatocytes with T0-901317 increases the concentration of mature sterol-regulatory element binding protein-1 (SREBP-1) in the nucleus and the acetylation of histone H3 and histone H4 at the ACCα LXR response unit. These results indicate that T0-901317 increases hepatic ACCα transcription by directly activating LXR•retinoid X receptor (RXR) heterodimers and by increasing the activity of an accessory transcription factor (SREBP-1) that enhances ligand induced-LXR•RXR activity.http://www.sciencedirect.com/science/article/pii/S0022227520433814fatty acid synthesissterol-regulatory element binding proteinthyroid hormonechickenhistone acetylation |
| spellingShingle | Saswata Talukdar F. Bradley Hillgartner The mechanism mediating the activation of acetyl-coenzyme A carboxylase-α gene transcription by the liver X receptor agonist T0-901317 Journal of Lipid Research fatty acid synthesis sterol-regulatory element binding protein thyroid hormone chicken histone acetylation |
| title | The mechanism mediating the activation of acetyl-coenzyme A carboxylase-α gene transcription by the liver X receptor agonist T0-901317 |
| title_full | The mechanism mediating the activation of acetyl-coenzyme A carboxylase-α gene transcription by the liver X receptor agonist T0-901317 |
| title_fullStr | The mechanism mediating the activation of acetyl-coenzyme A carboxylase-α gene transcription by the liver X receptor agonist T0-901317 |
| title_full_unstemmed | The mechanism mediating the activation of acetyl-coenzyme A carboxylase-α gene transcription by the liver X receptor agonist T0-901317 |
| title_short | The mechanism mediating the activation of acetyl-coenzyme A carboxylase-α gene transcription by the liver X receptor agonist T0-901317 |
| title_sort | mechanism mediating the activation of acetyl coenzyme a carboxylase α gene transcription by the liver x receptor agonist t0 901317 |
| topic | fatty acid synthesis sterol-regulatory element binding protein thyroid hormone chicken histone acetylation |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520433814 |
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