Calcium-mediated histone modifications regulate alternative splicing in cardiomyocytes
Open accessAbstract
Significance: Calcium is an important intracellular second messenger that regulates many biological processes. Many extracellular environmental cues lead to cellular calcium-level changes, which impact on the output of gene expression. 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. Our studies demonstrate that in these cells a network of alternatively spliced exons exists, which responds to the altered calcium levels by changing their splicing patterns. Our studies further elucidate an epigenetic regulatory mechanism, triggered by calcium signaling pathways, that leads to histone hyperacetylation along gene bodies, which increases the transcriptional elongation rate of RNA polymerase II and impacts alternative splicing.
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RNA Pol II speed can vary on individual genes or downstream of genes in response to different stimuli.
“Moreover, we and others have shown that RNA Pol II speed can vary on individual genes or downstream of genes in response to different stimuli (Schor et al, 2009; Schor et al, 2013; Sharma et al, 2014; Muniz et al, 2017).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Sharma et al, 2014
Changes in RNA Pol II velocity measured in response to cell depolarization and cell differentiation regulate alternative splicing and thus RNA identity.
“Indeed, changes in RNA Pol II velocity measured in response to cell depolarization and cell differentiation regulate alternative splicing and thus RNA identity (Schor et al, 2009; Schor et al, 2013; Sharma et al, 2014).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Sharma et al, 2014
A reduction in the level of class II HDACs on specific genes and increased H3 and H4 acetylation correlate with faster RNA Pol II transcription on these genes.
“For instance, a reduction in the level of class II HDACs on specific genes and increased H3 and H4 acetylation correlate with faster RNA Pol II transcription on these genes (Sharma et al, 2014).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Sharma et al, 2014
RNA Pol II velocity changes around alternatively spliced exons in specific genes, in response to cell depolarization and cellular differentiation.
“Second, RNA Pol II velocity changes around alternatively spliced exons in specific genes, in response to cell depolarization and cellular differentiation (Schor et al, 2009; Schor et al, 2013; Sharma et al, 2014).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Sharma et al, 2014
Local changes of histone modifications such as acetylation or methylation and RNA Pol II speed occur on alternative spliced exons during cell response to depolarization and differentiation.
“Along the same lines, local changes of histone modifications such as acetylation or methylation and RNA Pol II speed occur on alternative spliced exons during cell response to depolarization and differentiation (Schor et al, 2009; Schor et al, 2013; Sharma et al, 2014).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Sharma et al, 2014
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References 75 · Cited by 59
- Authors
- Sharma, A., Nguyen, H., Geng, C., Hinman, M. N., Luo, G., & Lou, H.
- Affiliations
- Department of Genetics and Genome Sciences,
- Case Comprehensive Cancer Center (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-11-03
- Volume
- 111
- Issue
- 46
- Pages
- E4920-8
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4246288
- OpenAlex
- W2076004517
- Cited by
- 59
- References
- 75
- Citations by year
- 2025: 4 · 2024: 5 · 2023: 4 · 2022: 6 · 2021: 6 · 2020: 8 · 2019: 6 · 2018: 3 · 2017: 7 · 2016: 5 · 2015: 4 · 2013: 1
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS) (NS049103)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- calcium signaling, alternative splicing, histone modifications, histone acetylation, histone deacetylase, histone acetyltransferase, exon skipping, transcription elongation, RNA polymerase II, cardiomyocytes, embryonic stem cell-derived cardiomyocytes
- MeSH terms
- Acetylation, Animals, Exons, Gene Expression Regulation, Histone Deacetylases, Histones, Potassium Chloride, Protein Processing, Post-Translational, RNA Polymerase II, RNA, Messenger, Signal Transduction, Genes, Neurofibromatosis 1, Alternative Splicing, Calcium Signaling, Neurofibromin 1, Myocytes, Cardiac, RNA, Small Interfering, Protein Kinase Inhibitors, TRPP Cation Channels, Mice, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Real-Time Polymerase Chain Reaction, Transcription Elongation, Genetic
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