Thyroid hormone regulates carnitine palmitoyltransferase Iα gene expression through elements in the promoter and first intron

Michelle S. Jansen, George Cook, Shulan Song, Edwards Park

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Carnitine palmitoyltransferase I (CPT-I) catalyzes the transfer of long chain fatty acyl groups from CoA to carnitine for translocation across the mitochondrial inner membrane. CPT-Iα is a key regulatory enzyme in the oxidation of fatty acids in the liver. CPT-Iα is expressed in all tissues except skeletal muscle and adipose tissue, which express CPT-Iβ. Expression of CPT-Iα mRNA and enzyme activity are elevated in the liver in hyperthyroidism, fasting, and diabetes. CPT-Iα mRNA abundance is increased 40-fold in the liver of hyperthyroid compared with hypothyroid rats. Here, we examine the mechanisms by which thyroid hormone (T3) stimulates CPT-Iα gene expression. Four potential T3 response elements (TRE), which contain direct repeats separated by four nucleotides, are located 3000-4000 base pairs 5' to the start site of transcription in the CPT-Iα gene. However, only one of these elements functions as a TRE. This TRE binds the T3 receptor as well as other nuclear proteins. Surprisingly, the first intron of the CPT-Iα gene is required for the T3 induction of CPT-Iα expression, but this region of the gene does not contain a TRE. In addition, we show that CPT-Iα is induced by T3 in cell lines of hepatic origin but not in nonhepatic cell lines.

Original languageEnglish (US)
Pages (from-to)34989-34997
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number45
DOIs
StatePublished - Nov 10 2000

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Carnitine O-Palmitoyltransferase
Thyroid Hormones
Gene expression
Introns
Gene Expression
Response Elements
Liver
Genes
Hyperthyroidism
Cells
Tissue
Cell Line
Thyroid Hormone Receptors
Acyl Coenzyme A
Messenger RNA
Carnitine
Nucleic Acid Repetitive Sequences
Transcription Initiation Site
Enzyme activity
Mitochondrial Membranes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Thyroid hormone regulates carnitine palmitoyltransferase Iα gene expression through elements in the promoter and first intron. / Jansen, Michelle S.; Cook, George; Song, Shulan; Park, Edwards.

In: Journal of Biological Chemistry, Vol. 275, No. 45, 10.11.2000, p. 34989-34997.

Research output: Contribution to journalArticle

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