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Human spot 14 glucose and thyroid hormone response: characterization and thyroid hormone response element
Mark C Campbell1, Grant W Anderson, Cary N Mariash
1University of Endocrinology and Diabetes, Department of Medicine, Univerisity of Minnesota, Minneapolis, Minnesota 55455, USA.
Endocrinology
|September 10, 2003
Summary
Human Spot 14 gene regulation differs from rats, showing greater thyroid hormone response. A specific DNA region binds thyroid hormone receptors, suggesting species-specific adaptations in lipogenesis.
Area of Science:
- Molecular Biology
- Genetics
- Endocrinology
Background:
- Spot 14 protein regulates lipogenesis and is stimulated by thyroid hormone.
- Understanding human Spot 14 gene regulation is crucial, especially given its location on a chromosome linked to obesity.
Purpose of the Study:
- To investigate the thyroid hormone responsivity of the human Spot 14 promoter.
- To identify regulatory elements involved in human Spot 14 gene expression.
Main Methods:
- Cloning of the human Spot 14 gene.
- Analysis of human and rat Spot 14 promoter activity in response to thyroid hormone.
- Deletional analysis and electrophoretic mobility shift assays (EMSAs).
- Site-directed mutagenesis to identify thyroid hormone response elements.
Main Results:
- The human Spot 14 promoter exhibits a significantly greater thyroid hormone response compared to the rat ortholog.
- A 774-bp region (-2700 to -2000) is essential for this response.
- A 146-bp fragment binds a thyroid hormone receptor beta 1 (TRbeta1)-retinoid X receptor heterodimer.
- A novel DR-4 thyroid hormone response element was identified in the human promoter.
Conclusions:
- The human Spot 14 promoter possesses distinct regulatory mechanisms compared to the rat.
- Differences in thyroid hormone response elements may confer species-specific advantages related to nutritional and physiological niches.