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Published on: November 15, 2013
Liver X receptor-alpha gene expression is positively regulated by thyroid hormone
Koshi Hashimoto1, Shunichi Matsumoto, Masanobu Yamada
1Department of Medicine and Molecular Science, Graduate School of Medicine, Gunma University, 3-39-22 Showa-machi Maebashi, Gunma, Japan 371-8511. khashi@med.gunma-u.ac.jp
Endocrinology
|July 14, 2007
Summary
Thyroid hormone (T3) up-regulates liver X receptor-alpha (LXR-alpha) mRNA expression and promoter activity in mammals. This cross-talk between thyroid hormone receptors (TRs) and LXR-alpha offers a potential therapeutic target for dyslipidemia and atherosclerosis.
Area of Science:
- Molecular Endocrinology
- Nuclear Receptor Signaling
Background:
- Liver X receptors (LXRs) and thyroid hormone receptors (TRs) are nuclear receptors that interact transcriptionally.
- LXRs and TRs share DNA binding sites, suggesting potential cross-talk in gene regulation.
Purpose of the Study:
- To investigate the regulatory relationship between thyroid hormone (T3) and liver X receptor-alpha (LXR-alpha) expression and promoter activity.
- To determine if TRs modulate LXR-alpha gene transcription.
Main Methods:
- Quantitative mRNA expression analysis in mouse liver.
- Luciferase reporter assays to assess promoter activity.
- Analysis of promoter deletion mutants.
- Electrophoretic Mobility Shift Assays (EMSA).
- Chromatin Immunoprecipitation (ChIP) assays.
Main Results:
- Thyroid hormone (T3) significantly increased mouse LXR-alpha mRNA levels in the liver.
- TR-beta1 positively regulated mouse LXR-alpha gene transcription.
- TR-beta1 and retinoid X receptor-alpha were recruited to a specific region (site A) of the LXR-alpha promoter, suggesting indirect DNA binding.
- T3 also enhanced human LXR-alpha gene expression and promoter activity.
Conclusions:
- LXR-alpha mRNA expression and promoter activity are positively regulated by TR-beta1 and thyroid hormone at the transcriptional level.
- This cross-talk between LXR-alpha and TR-beta1 represents a novel regulatory mechanism.
- The findings suggest a potential therapeutic target for dyslipidemia and atherosclerosis.
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