A thyroid hormone response unit formed between the promoter and first intron of the carnitine palmitoyltransferase-Iα gene mediates the liver-specific induction by thyroid hormone

Loretta Jackson-Hayes, Shulan Song, Eduard N. Lavrentyev, Michelle S. Jansen, F. Bradley Hillgartner, Liquin Tian, Philip A. Wood, George Cook, Edwards Park

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Carnitine palmitoyltransferase-I (CPT-I) catalyzes the rate-controlling step of fatty acid oxidation. CPT-I converts long-chain fatty acyl-CoAs to acylcarnitines for translocation across the mitochondrial membrane. The mRNA levels and enzyme activity of the liver isoform, CPT-Iα, are greatly increased in the liver of hyperthyroid animals. Thyroid hormone (T3) stimulates CPT-Iα 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-Iα promoter. In addition, elements in the first intron participate in the T3 induction of CPT-Iα gene expression, but the CPT-Iα 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-Iα. 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-Iα gene in vivo was shown by the chromatin immunoprecipitation assay. We determined that TR can physically interact with USF-1, USF-2, and C/EBPα. Transgenic mice were created that carry CPT-Iα-luciferase transgenes with or without the first intron of the CPT-Iα gene. In these mouse lines, the first intron is required for T3 induction as well as high levels of hepatic expression. Our data indicate that the T3 stimulates CPT-Iα 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.

Original languageEnglish (US)
Pages (from-to)7964-7972
Number of pages9
JournalJournal of Biological Chemistry
Volume278
Issue number10
DOIs
StatePublished - Mar 7 2003

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Carnitine O-Palmitoyltransferase
Thyroid Hormones
Liver
Introns
Genes
Upstream Stimulatory Factors
CCAAT-Enhancer-Binding Proteins
Thyroid Hormone Receptors
Response Elements
Gene expression
Gene Expression
Sequence Deletion
Chromatin Immunoprecipitation
Enzyme activity
Mitochondrial Membranes
Triiodothyronine
Hyperthyroidism
Transcription
Luciferases
Transgenes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

A thyroid hormone response unit formed between the promoter and first intron of the carnitine palmitoyltransferase-Iα gene mediates the liver-specific induction by thyroid hormone. / Jackson-Hayes, Loretta; Song, Shulan; Lavrentyev, Eduard N.; Jansen, Michelle S.; Hillgartner, F. Bradley; Tian, Liquin; Wood, Philip A.; Cook, George; Park, Edwards.

In: Journal of Biological Chemistry, Vol. 278, No. 10, 07.03.2003, p. 7964-7972.

Research output: Contribution to journalArticle

Jackson-Hayes, Loretta ; Song, Shulan ; Lavrentyev, Eduard N. ; Jansen, Michelle S. ; Hillgartner, F. Bradley ; Tian, Liquin ; Wood, Philip A. ; Cook, George ; Park, Edwards. / A thyroid hormone response unit formed between the promoter and first intron of the carnitine palmitoyltransferase-Iα gene mediates the liver-specific induction by thyroid hormone. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 10. pp. 7964-7972.
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AU - Jansen, Michelle S.

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AU - Tian, Liquin

AU - Wood, Philip A.

AU - Cook, George

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