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Cardiac myosin heavy chain gene regulation by thyroid hormone involves altered histone modifications
F Haddad1, W Jiang, P W Bodell
1Department of Physiology and Biophysics, University of California, Irvine, California 92697-4560, USA. fhaddad@uci.edu
American Journal of Physiology. Heart and Circulatory Physiology
|September 14, 2010
Summary
Thyroid hormone influences cardiac myosin heavy chain (MHC) gene expression through epigenetic modifications. This study reveals specific histone changes linked to MHC gene switching in altered thyroid states.
Area of Science:
- Molecular Biology
- Epigenetics
- Cardiovascular Research
Background:
- Thyroid hormone (T3) regulates cardiac myosin heavy chain (MHC) gene expression antithetically, a process not fully understood.
- Epigenetic mechanisms, including histone modifications and noncoding RNAs, are implicated in T3-mediated MHC gene regulation.
Purpose of the Study:
- To investigate how altered thyroid states (hypothyroid and hyperthyroid) induce specific histone modifications in cardiac MHC gene chromatin.
- To identify epigenetic events correlating with cardiac MHC gene switching in response to thyroid hormone imbalances.
Main Methods:
- Hypothyroid and hyperthyroid states were induced in rats using propylthiouracil (PTU) and T3, respectively.
- Cardiac left ventricles were analyzed for pre-mRNA expression and chromatin enrichment of histone modifications (H3K9/14ac, H3K4me3, H3K9me, H4K20me1) via chromatin immunoprecipitation quantitative PCR.
Main Results:
- Histone modifications H3K9/14ac and H3K4me3 decreased with PTU treatment at the alpha-MHC promoter and intergenic regions.
- H3K4me3 enrichment correlated with beta-MHC promoter activity in both PTU and T3 groups, while H3K9/14ac was repressed by T3.
- Specific histone marks (H3K9me, H4K20me1) showed differential enrichment patterns associated with altered thyroid states and MHC gene promoters.
Conclusions:
- Specific epigenetic modifications, including distinct histone marks, are modulated by thyroid hormone status.
- These epigenetic changes provide a mechanism linking altered thyroid states to the observed cardiac MHC gene switching.
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