ArticleEndocrinology2010
Repression of cardiac phospholamban gene expression is mediated by thyroid hormone receptor-{alpha}1 and involves targeted covalent histone modifications.
Article in Endocrinology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- American Thyroid Association Guide to investigating thyroid hormone economy and action in rodent and cell models.Thyroid : official journal of the American Thyroid Association · 2014Guideline
- Triiodothyronine supplementation and cytokines during cardiopulmonary bypass in infants and children.The Journal of thoracic and cardiovascular surgery · 2012Trial
- Genetic landscape of phospholamban cardiomyopathies.Frontiers in cell and developmental biology · 2025Review
- Synergistic effects of hormones on structural and functional maturation of cardiomyocytes and implications for heart regeneration.Cellular and molecular life sciences : CMLS · 2023Review
- Thyroid hormone-dependent regulation of metabolism and heart regeneration.The Journal of endocrinology · 2022Review
- Physiologic Significance of Epigenetic Regulation of Thyroid Hormone Target Gene Expression.European thyroid journal · 2020Review
- HuR regulates phospholamban expression in isoproterenol-induced cardiac remodelling.Cardiovascular research · 2020Article
- Maternal and fetal thyroid dysfunction following porcine reproductive and respiratory syndrome virus2 infection.Veterinary research · 2020Article
- Cardiomyocyte Proliferation and Maturation: Two Sides of the Same Coin for Heart Regeneration.Frontiers in cell and developmental biology · 2020Review
- Regulation of cardiac transcription by thyroid hormone and Med13.Journal of molecular and cellular cardiology · 2019Article
- Novel Insight Into the Epigenetic and Post-transcriptional Control of Cardiac Gene Expression by Thyroid Hormone.Frontiers in endocrinology · 2019Review
- MuRF1 mono-ubiquitinates TRα to inhibit T3-induced cardiac hypertrophy in vivo.Journal of molecular endocrinology · 2016Article
- PHD2/3-dependent hydroxylation tunes cardiac response to β-adrenergic stress via phospholamban.The Journal of clinical investigation · 2015Article
- The emerging role of TRα1 in cardiac repair: potential therapeutic implications.Oxidative medicine and cellular longevity · 2014Review
- Inhibition of thyroid hormone receptor α1 impairs post-ischemic cardiac performance after myocardial infarction in mice.Molecular and cellular biochemistry · 2013Article
- Thyroid hormone is required for growth adaptation to pressure load in the ovine fetal heart.Experimental physiology · 2013Article
- Molecular basis of physiological heart growth: fundamental concepts and new players.Nature reviews. Molecular cell biology · 2013Review
- New insights into the role of thyroid hormone in cardiac remodeling: time to reconsider?Heart failure reviews · 2011Review
- Thyroid hormone can favorably remodel the diabetic myocardium after acute myocardial infarction.Molecular and cellular biochemistry · 2010Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Phospholamban (PLB) is a critical regulator of Ca(2+) cycling in heart muscle cells, and its gene expression is markedly down-regulated by T(3). Nonetheless, little is known about the molecular mechanisms of T(3)-dependent gene silencing in cardiac muscle, and it remains unclear whether thyroid hormone receptors (TRs) directly bind at the PLB gene in vivo and facilitate transcriptional repression. To investigate the regulatory role of TRs in PLB transcription, we used a physiological murine heart muscle cell line (HL-1) that retains cardiac electrophysiological properties, expresses both TRalpha1 and TRbeta1 subtypes, and exhibits T(3)-dependent silencing of PLB expression. By performing RNA interference assays with HL-1 cells, we found that TRalpha1, but not TRbeta1, is essential for T(3)-dependent PLB gene repression. Interestingly, a PLB reporter gene containing only the core promoter sequences -156 to +64 displayed robust T(3)-dependent silencing in HL-1 cells, thus suggesting that transcriptional repression is facilitated by TRalpha1 via the PLB core promoter, a regulatory region highly conserved in mammals. Consistent with this notion, chromatin immunoprecipitation and in vitro binding assays show that TRalpha1 directly binds at the PLB core promoter region. Furthermore, addition of T(3) triggered alterations in covalent histone modifications at the PLB promoter that are associated with gene silencing, namely a pronounced decrease in both histone H3 acetylation and histone H3 lysine 4 methylation. Taken together, our data reveal that T(3)-dependent repression of PLB in cardiac myocytes is directly facilitated by TRalpha1 and involves the hormone-dependent recruitment of histone-modifying enzymes associated with transcriptional silencing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.