ArticleCirculation. Heart failure2019
Recruitment of RNA Polymerase II to Metabolic Gene Promoters Is Inhibited in the Failing Heart Possibly Through PGC-1α (Peroxisome Proliferator-Activated Receptor-γ Coactivator-1α) Dysregulation.
Article in Circulation. Heart failure, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Oxidative Stress, Mitochondrial Quality Control, Autophagy, and Sirtuins in Heart Failure.International journal of molecular sciences · 2025Review
- The Role of AMPKα in the Mechanism of Development and Treatment of Heart Failure.Reviews in cardiovascular medicine · 2025Review
- Peroxisome proliferator‑activated receptor γ coactivator‑1α in heart disease (Review).Molecular medicine reports · 2025Review
- Omega-3 Fatty Acids Modify Drp1 Expression and Activate the PINK1-Dependent Mitophagy Pathway in the Kidney and Heart of Adenine-Induced Uremic Rats.Biomedicines · 2024Article
- Human RNA Polymerase II Segregates from Genes and Nascent RNA and Transcribes in the Presence of DNA-Bound dCas9.International journal of molecular sciences · 2024Article
- Mitochondrial quality control in human health and disease.Military Medical Research · 2024Review
- Epigallocatechin-3-gallate restores mitochondrial homeostasis impairment by inhibiting HDAC1-mediated NRF1 histone deacetylation in cardiac hypertrophy.Molecular and cellular biochemistry · 2024Article
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal transduction and targeted therapy · 2024Review
- SMYD1a protects the heart from ischemic injury by regulating OPA1-mediated cristae remodeling and supercomplex formation.Basic research in cardiology · 2023Article
- The role of m5C methyltransferases in cardiovascular diseases.Frontiers in cardiovascular medicine · 2023Review
- Novel Therapeutic Approaches Enhance PGC1-alpha to Reduce Oxidant Stress-Inflammatory Signaling and Improve Functional Recovery in Hibernating Myocardium.Antioxidants (Basel, Switzerland) · 2022Review
- Article
- PERM1 regulates energy metabolism in the heartFrontiers in cardiovascular medicine · 2022Article
- Estrogen signaling as a bridge between the nucleus and mitochondria in cardiovascular diseases.Frontiers in cell and developmental biology · 2022Review
- PGC-1Frontiers in cell and developmental biology · 2022Review
- Article
- Moderate Exercise in Spontaneously Hypertensive Rats Is Unable to Activate the Expression of Genes Linked to Mitochondrial Dynamics and Biogenesis in Cardiomyocytes.Frontiers in endocrinology · 2020Article
- Perm1 regulates cardiac energetics as a downstream target of the histone methyltransferase Smyd1.PloS one · 2020Article
- Multiple Levels of PGC-1α Dysregulation in Heart Failure.Frontiers in cardiovascular medicine · 2020Review
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 3 countries.
Funding
Abstract
backgroundProper dynamics of RNA polymerase II, such as promoter recruitment and elongation, are essential for transcription. PGC-1α (peroxisome proliferator-activated receptor [PPAR]-γ coactivator-1α), also termed PPARGC1a, is a transcriptional coactivator that stimulates energy metabolism, and PGC-1α target genes are downregulated in the failing heart. However, whether the dysregulation of polymerase II dynamics occurs in PGC-1α target genes in heart failure has not been defined. METHODS AND
resultsChromatin immunoprecipitation-sequencing revealed that reduced promoter occupancy was a major form of polymerase II dysregulation on PGC-1α target metabolic gene promoters in the pressure-overload-induced heart failure model. PGC-1α-cKO (cardiac-specific PGC-1α knockout) mice showed phenotypic similarity to the pressure-overload-induced heart failure model in wild-type mice, such as contractile dysfunction and downregulation of PGC-1α target genes, even under basal conditions. However, the protein levels of PGC-1α were neither changed in the pressure-overload model nor in human failing hearts. Chromatin immunoprecipitation assays revealed that the promoter occupancy of polymerase II and PGC-1α was consistently reduced both in the pressure-overload model and PGC-1α-cKO mice. In vitro DNA binding assays using an endogenous PGC-1α target gene promoter sequence confirmed that PGC-1α recruits polymerase II to the promoter.
conclusionsThese results suggest that PGC-1α promotes the recruitment of polymerase II to the PGC-1α target gene promoters. Downregulation of PGC-1α target genes in the failing heart is attributed, in part, to a reduction of the PGC-1α occupancy and the polymerase II recruitment to the promoters, which might be a novel mechanism of metabolic perturbations in the failing heart.
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