ArticleNucleic acids research2019
Chromatin remodeler Ep400 ensures oligodendrocyte survival and is required for myelination in the vertebrate central nervous system.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 39 citations in OpenAlex.
- Paediatric Therapeutic Development Workshop on rhabdoid tumours.British journal of cancer · 2026Review
- ACSS2 maintains oligodendrocyte progenitor cell pool and is required for myelination during development and aging.Nature aging · 2026Article
- Chromatin remodeling activity of EP400 safeguards chromosomal stability by preventing CENP-A mislocalization.Cell reports · 2025Article
- Review
- Article
- Dysregulation of myelination-related genes in schizophrenia.Journal of neurochemistry · 2024Review
- Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex.Science (New York, N.Y.) · 2024Article
- Identifying unstable CNG repeat loci in the human genome: a heuristic approach and implications for neurological disorders.Human genome variation · 2024Article
- Sox10 Activity and the Timing of Schwann Cell Differentiation Are Controlled by a Tle4-Dependent Negative Feedback Loop.International journal of molecular sciences · 2024Article
- Chromatin Modifier EP400 Regulates Oocyte Quality and Zygotic Genome Activation in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Article
- The Tip60/Ep400 chromatin remodeling complex impacts basic cellular functions in cranial neural crest-derived tissue during early orofacial development.International journal of oral science · 2023Article
- KLF9 and KLF13 transcription factors boost myelin gene expression in oligodendrocytes as partners of SOX10 and MYRF.Nucleic acids research · 2022Article
- Transient regulation of focal adhesion via Tensin3 is required for nascent oligodendrocyte differentiation.eLife · 2022Article
- The Role of the Histone Variant H2A.Z in Metazoan Development.Journal of developmental biology · 2022Review
- [A review on the genetic mechanism of chromatin remodeling in children with neurodevelopmental disorders].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2021Review
- A unique missense variant in the E1A-binding protein P400 gene is implicated in schizophrenia by whole-exome sequencing and mutant mouse models.Translational psychiatry · 2021Article
- Oligodendroglial Epigenetics, from Lineage Specification to Activity-Dependent Myelination.Life (Basel, Switzerland) · 2021Review
- Defining the Dynamic Regulation of O-GlcNAc Proteome in the Mouse Cortex---the O-GlcNAcylation of Synaptic and Trafficking Proteins Related to Neurodegenerative Diseases.Frontiers in aging · 2021Article
- Conditional Loss of BAF (mSWI/SNF) Scaffolding Subunits Affects Specification and Proliferation of Oligodendrocyte Precursors in Developing Mouse Forebrain.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Differentiating oligodendrocytes generate myelin to ensure rapid saltatory conduction in the vertebrate central nervous system. Although oligodendroglial differentiation and myelination are accompanied by dramatic chromatin reorganizations, previously studied chromatin remodelers had only limited direct effects on the process. To study the functional significance of chromatin changes for myelination and identify relevant remodelers, we deleted Ep400, the central ATP-hydrolyzing subunit of the TIP60/EP400 complex, at defined times of mouse oligodendrocyte development. Whereas Ep400-deficient oligodendrocyte precursors develop normally, terminal differentiation and myelination are dramatically impaired. Mechanistically, Ep400 interacts with transcription factor Sox10, binds to regulatory regions of the Myrf gene and is required to induce this central transcriptional regulator of the myelination program. In addition to reduced and aberrant myelin formation, oligodendrocytes exhibit increased DNA damage and apoptosis so that numbers never reach wildtype levels during the short lifespan of Ep400-deficient mice. Ep400 deletion in already mature oligodendrocytes remains phenotypically inapparent arguing that Ep400 is dispensable for myelin maintenance. Given its essential function in myelin formation, modulation of Ep400 activity may be beneficial in conditions such as multiple sclerosis where this process is compromised.
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