ArticleProceedings of the National Academy of Sciences of the United States of America2014
Calcium-mediated histone modifications regulate alternative splicing in cardiomyocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Gene expression regulation by CaCellular & molecular biology letters · 2026Pooled it
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- Structural basis of RECQL5-induced RNA polymerase II transcription braking and subsequent reactivation.Nature structural & molecular biology · 2025Article
- Impact of dcEF on microRNA profiles in glioblastoma and exosomes using a novel microfluidic bioreactor.Biomicrofluidics · 2024Article
- Depolarization induces calcium-dependent BMP4 release from mouse embryonic palate mesenchymal cells.Nature communications · 2024Article
- Ginsenoside Rb2 inhibits p300-mediated SF3A2 acetylation at lysine 10 to promote Fscn1 alternative splicing against myocardial ischemic/reperfusion injury.Journal of advanced research · 2024Article
- Neural Tissue-Like, not Supraphysiological, Electrical Conductivity Stimulates Neuronal Lineage Specification through Calcium Signaling and Epigenetic Modification.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Establishment and Maintenance of Heat-Stress Memory in Plants.International journal of molecular sciences · 2024Review
- Distinct calcium sources regulate temporal profiles of NMDAR and mGluR-mediated protein synthesis.Life science alliance · 2024Article
- End binding-3 inhibitor activates regenerative program in age-related macular degeneration.Cell reports. Medicine · 2023Article
- Antibodies to variable surface antigens induce antigenic variation in the intestinal parasite Giardia lamblia.Nature communications · 2023Article
- It's a DoG-eat-DoG world-altered transcriptional mechanisms drive downstream-of-gene (DoG) transcript production.Molecular cell · 2022Review
- Alternative splicing regulation of membrane trafficking genes during myogenesis.RNA (New York, N.Y.) · 2022Article
- Targeted transcript analysis in muscles from patients with genetically diverse congenital myopathies.Brain communications · 2022Article
- RNA polymerase II speed: a key player in controlling and adapting transcriptome composition.The EMBO journal · 2021Review
- Mitochondria signaling to the epigenome: A novel role for an old organelle.Free radical biology & medicine · 2021Review
- RNA splicing and aggregate gene expression differences in lung squamous cell carcinoma between patients of West African and European ancestry.Lung cancer (Amsterdam, Netherlands) · 2021Article
- High salt intake induces collecting duct HDAC1-dependent NO signaling.American journal of physiology. Renal physiology · 2021Article
- Calcium dynamics and chromatin remodelling underlie heterogeneity in prolactin transcription.Journal of molecular endocrinology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
In cardiomyocytes, calcium is known to control gene expression at the level of transcription, whereas its role in regulating alternative splicing has not been explored. Here we report that, in mouse primary or embryonic stem cell-derived cardiomyocytes, increased calcium levels induce robust and reversible skipping of several alternative exons from endogenously expressed genes. Interestingly, we demonstrate a calcium-mediated splicing regulatory mechanism that depends on changes of histone modifications. Specifically, the regulation occurs through changes in calcium-responsive kinase activities that lead to alterations in histone modifications and subsequent changes in the transcriptional elongation rate and exon skipping. We demonstrate that increased intracellular calcium levels lead to histone hyperacetylation along the body of the genes containing calcium-responsive alternative exons by disrupting the histone deacetylase-to-histone acetyltransferase balance in the nucleus. Consequently, the RNA polymerase II elongation rate increases significantly on those genes, resulting in skipping of the alternative exons. These studies reveal a mechanism by which calcium-level changes in cardiomyocytes impact on the output of gene expression through altering alternative pre-mRNA splicing patterns.
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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.