ArticleProceedings of the National Academy of Sciences of the United States of America2009
Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
169 citing papers in PubMed, 1 synthesis or guideline pooled it, 266 citations in OpenAlex.
- Meta-analysis of activated neurons reveals dynamic regulation of diverse classes of alternative splicing.Genome research · 2025Pooled it
- RNA splicing in health and disease.Molecular biomedicine · 2026Review
- Epigenetic regulation by gut microbiota-derived metabolites in celiac disease.Biochemistry and biophysics reports · 2026Review
- Combined single-cell profiling of chromatin-transcriptome and splicing across brain cell types, regions and disease state.Nature biotechnology · 2026Article
- HDAC Inhibition Reshapes Splicing of Synaptic Plasticity-Related Genes and Neural Network Dynamics.Cellular and molecular neurobiology · 2026Article
- RNA-binding proteins connect Exon usage to the chromatin.NAR genomics and bioinformatics · 2025Article
- Alternative splicing: from tumorigenesis to neoantigen-mediated cancer immunotherapy.Biomarker research · 2025Review
- DNA Methylation and Alternative Splicing Safeguard Genome and Transcriptome After a Retrotransposition Burst inInternational journal of molecular sciences · 2025Article
- Epigenetic Regulation and Therapeutic Targeting of Alternative Splicing Dysregulation in Cancer.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Physiological and pathological roles of the transcriptional kinases CDK12 and CDK13 in the central nervous system.Cell death and differentiation · 2025Review
- Emerging and re-emerging themes in co-transcriptional pre-mRNA splicing.Molecular cell · 2024Review
- Epigenetic control of adaptive or homeostatic splicing during interval-training activities.Nucleic acids research · 2024Article
- Co-transcriptional gene regulation in eukaryotes and prokaryotes.Nature reviews. Molecular cell biology · 2024Review
- Age-dependent regulation of ELP1 exon 20 splicing in Familial Dysautonomia by RNA Polymerase II kinetics and chromatin structure.PloS one · 2024Article
- Disentangling specific and unspecific components of innate immune memory in a copepod-tapeworm system.Frontiers in immunology · 2024Article
- Beyond transcription: compelling open questions in plant RNA biology.The Plant cell · 2023Article
- The physiology of alternative splicing.Nature reviews. Molecular cell biology · 2023Review
- A novel SATB1 protein isoform with different biophysical properties.Frontiers in cell and developmental biology · 2023Article
- Histone deacetylase inhibitors improve antisense-mediated exon-skipping efficacy inMolecular therapy. Nucleic acids · 2022Article
- Histone Marks-Dependent Effect on Alternative Splicing: New Perspectives for Targeted Splicing Modulation in Cancer?International journal of molecular sciences · 2022Review
109 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
In search for physiological pathways affecting alternative splicing through its kinetic coupling with transcription, we found that membrane depolarization of neuronal cells triggers the skipping of exon 18 from the neural cell adhesion molecule (NCAM) mRNA, independently of the calcium/calmodulin protein kinase IV pathway. We show that this exon responds to RNA polymerase II elongation, because its inclusion is increased by a slow polymerase II mutant. Depolarization affects the chromatin template in a specific way, by causing H3K9 hyper-acetylation restricted to an internal region of the NCAM gene surrounding the alternative exon. This intragenic histone hyper-acetylation is not paralleled by acetylation at the promoter, is associated with chromatin relaxation, and is linked to H3K36 tri-methylation. The effects on acetylation and splicing fully revert when the depolarizing conditions are withdrawn and can be both duplicated and potentiated by the histone deacetylase inhibitor trichostatin A. Our results are consistent with a mechanism involving the kinetic coupling of splicing and transcription in response to depolarization through intragenic epigenetic changes on a gene that is relevant for the differentiation and function of neuronal cells.
Indexed as
Identifiers
What OpenQuestion holds
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.