ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2010
Alternative splicing of the histone demethylase LSD1/KDM1 contributes to the modulation of neurite morphogenesis in the mammalian nervous system.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers.
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Who cites it
107 citing papers in PubMed, 174 citations in OpenAlex.
- Distinct cell states define larval and adult body plans in a hemichordate.Nature communications · 2026Article
- The functional landscape of alternative splicing in hematopoietic lineage commitment.Nature communications · 2026Article
- CRB2 Activates an Epigenetic Axis to Promote Ferroptosis in Head and Neck Squamous Cell Carcinoma.Cancer research · 2026Article
- Ethanol selectively disrupts neuronal microexon regulation and chromatin marks in PC12 cells.Frontiers in cellular neuroscience · 2026Article
- Transcript Imbalance from TENM4 Exon Skipping: Effects on Epilepsy and Genetic Pleiotropy.Molecular neurobiology · 2025Article
- Phenotypic impact of individual conserved neuronal microexons and their master regulators in zebrafish.eLife · 2025Article
- Molecular Consequences of a Missense PHF21A Variant, c.1285G > A, Associated With Syndromic Neurodevelopmental Disorder.Cellular and molecular neurobiology · 2025Article
- CoREST in pieces: Dismantling the CoREST complex for cancer therapy and beyond.Science advances · 2025Review
- The multifaceted role of post-translational modifications of LSD1 in cellular processes and disease pathogenesis.Genes & diseases · 2025Review
- Covalent adduct Grob fragmentation underlies LSD1 demethylase-specific inhibitor mechanism of action and resistance.Nature communications · 2025Article
- Review
- Coordinated neuron-specific splicing events restrict nucleosome engagement of the LSD1 histone demethylase complex.Cell reports · 2025Article
- O-GlcNAc transferase congenital disorder of glycosylation (OGT-CDG): Potential mechanistic targets revealed by evaluating the OGT interactome.The Journal of biological chemistry · 2024Review
- Asynchronous microexon splicing ofbioRxiv : the preprint server for biology · 2024Article
- LSD1 Regulates Neurogenesis in Human Neural Stem Cells Through the Repression of Human-Enriched Extracellular Matrix and Cell Adhesion Genes.Stem cells (Dayton, Ohio) · 2024Article
- Post-transcriptional regulation of the transcriptional apparatus in neuronal development.Frontiers in molecular neuroscience · 2024Review
- Fluorescent Reporter Systems to Investigate Chromatin Effector Proteins in Living Cells.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Review
- Evolution of lysine-specific demethylase 1 and REST corepressor gene families and their molecular interaction.Communications biology · 2023Article
- LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice.Nature communications · 2023Article
47 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
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Abstract
A variety of chromatin remodeling complexes are thought to orchestrate transcriptional programs that lead neuronal precursors from earliest commitment to terminal differentiation. Here we show that mammalian neurons have a specialized chromatin remodeling enzyme arising from a neurospecific splice variant of LSD1/KDM1, histone lysine specific demethylase 1, whose demethylase activity on Lys4 of histone H3 has been related to gene repression. We found that alternative splicing of LSD1 transcript generates four full-length isoforms from combinatorial retention of two identified exons: the 4 aa exon E8a is internal to the amine oxidase domain, and its inclusion is restricted to the nervous system. Remarkably, the expression of LSD1 splice variants is dynamically regulated throughout cortical development, particularly during perinatal stages, with a progressive increase of LSD1 neurospecific isoforms over the ubiquitous ones. Notably, the same LSD1 splice dynamics can be fairly recapitulated in cultured cortical neurons. Functionally, LSD1 isoforms display in vitro a comparable demethylase activity, yet the inclusion of the sole exon E8a reduces LSD1 repressor activity on a reporter gene. Additional distinction among isoforms is supported by the knockdown of neurospecific variants in cortical neurons resulting in the inhibition of neurite maturation, whereas overexpression of the same variants enhances it. Instead, perturbation of LSD1 isoforms that are devoid of the neurospecific exon elicits no morphogenic effect. Collectively, results demonstrate that the arousal of neuronal LSD1 isoforms pacemakes early neurite morphogenesis, conferring a neurospecific function to LSD1 epigenetic activity.
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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.