| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print December 19, 2002
Pharmacology, University of Tennessee, Memphis, TN 38163
Corresponding Author: epark{at}utmem.edu
Carnitine palmitoyltransferase-I (CPT-I) catalyzes the rate-controlling step of fatty acid oxidation. CPT-I converts long-chain fatty acyl-CoAs to acyl-carnitines for translocation across the mitochondrial membrane. The mRNA levels and enzyme activity of the liver isoform, CPT-I
J. Biol. Chem, 10.1074/jbc.M211062200
Submitted on October 29, 2002
Revised on December 16, 2002
Accepted on December 19, 2002
A thyroid hormone response unit formed between the promoter and first intron of the carnitine palmitoyltransferase-Ia gene mediates the liver specific induction by thyroid hormone
, are greatly increased in the liver of hyperthyroid animals. Thyroid hormone (T3) stimulates CPT-I transcription far more robustly in the liver than in non-hepatic tissues. We have shown that the thyroid hormone receptor (TR) binds to a thyroid hormone response element (TRE) located in the CPT-I promoter. In addition, elements in the first intron participate in the T3 induction of CPT-I gene expression, but the CPT-I intron alone cannot confer a T3 response. We found that deletion of sequences in the first intron between +653 and +744 decreased the T3 induction of CPT-I. Upstream stimulatory factor (USF) and CCAAT enhancer binding proteins (C/EBPs) bind to elements within this region, and these factors are required for the T3 response. The binding of TR and C/EBP to the CPT-I gene in vivo was shown by the chromatin immunoprecipitation assay. We determined that TR can physically interact with USF-1, USF-2 and C/EBP. Transgenic mice were created that carry CPT-I-Luciferase transgenes with or without the first intron of the CPT-I gene. In these mouse lines, the first intron is required for the T3 induction as well as high levels of hepatic expression. Our data indicate that the T3 stimulates CPT-I gene expression in the liver through a T3 response unit consisting of the TRE in the promoter and additional factors, C/EBP and USF, bound in the first intron.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  B. Desvergne, L. Michalik, and W. Wahli Transcriptional Regulation of Metabolism Physiol Rev, April 1, 2006; 86(2): 465 - 514. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Prieur, T. Huby, H. Coste, F. G. Schaap, M. J. Chapman, and J. C. Rodriguez Thyroid Hormone Regulates the Hypotriglyceridemic Gene APOA5 J. Biol. Chem., July 29, 2005; 280(30): 27533 - 27543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Zhang, K. Ma, S. Song, Marshall. B. Elam, G. A. Cook, and E. A. Park Peroxisomal Proliferator-activated Receptor-{gamma} Coactivator-1{alpha} (PGC-1{alpha}) Enhances the Thyroid Hormone Induction of Carnitine Palmitoyltransferase I (CPT-I{alpha}) J. Biol. Chem., December 24, 2004; 279(52): 53963 - 53971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-h. Shih, S.-L. Chen, C.-C. Yen, Y.-H. Huang, C.-d. Chen, Y.-S. Lee, and K.-h. Lin Thyroid Hormone Receptor-Dependent Transcriptional Regulation of Fibrinogen and Coagulation Proteins Endocrinology, June 1, 2004; 145(6): 2804 - 2814. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
