ArticleEpigenetics2018
DNMT1 modulates interneuron morphology by regulating Pak6 expression through crosstalk with histone modifications.
Article in Epigenetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Disease-Associated Mutations Impact DNA Methyltransferase 1 Function through Dynamic Allosteric Effects and Solvent Exposure.Journal of chemical theory and computation · 2026Article
- DNMT1-mediated regulation of somatostatin-positive interneuron migration impacts cortical architecture and function.Nature communications · 2025Article
- Rescuing DNMT1 fails to fully reverse the molecular and functional repercussions of its loss in mouse embryonic stem cells.Nucleic acids research · 2025Article
- The role of lncRNAs in the interplay of signaling pathways and epigenetic mechanisms in glioma.Epigenomics · 2025Review
- Bidirectional substance P signaling between periodontal ligament fibroblasts and sensory neurons under mechanical stress.Frontiers in molecular neuroscience · 2025Article
- DNMT1 SNPs (rs2114724 and rs2228611) associated with positive symptoms in Chinese patients with schizophrenia.Annals of general psychiatry · 2023Article
- GDF15 Promotes the Osteogenic Cell Fate of Periodontal Ligament Fibroblasts, thus Affecting Their Mechanobiological Response.International journal of molecular sciences · 2023Article
- Identification of molecular subtypes of ischaemic stroke based on immune-related genes and weighted co-expression network analysis.IET systems biology · 2023Article
- Oleic acid-related anti-inflammatory effects in force-stressed PdL fibroblasts are mediated by H3 lysine acetylation associated with alteredEpigenetics · 2022Article
- Regulatory mechanism and biological function of UHRF1-DNMT1-mediated DNA methylation.Functional & integrative genomics · 2022Review
- Dementia with Lewy bodies post-mortem brains reveal differentially methylated CpG sites with biomarker potential.Communications biology · 2022Article
- Article
- Role of DNMTs in the Brain.Advances in experimental medicine and biology · 2022Review
- Review
- The emerging role of chromatin remodelers in neurodevelopmental disorders: a developmental perspective.Cellular and molecular life sciences : CMLS · 2021Review
- DNA Methyltransferase 1 (DNMT1) Shapes Neuronal Activity of Human iPSC-Derived Glutamatergic Cortical Neurons.International journal of molecular sciences · 2021Article
- The Epigenome in Neurodevelopmental Disorders.Frontiers in neuroscience · 2021Review
- NeuronalEpigenetics · 2020Article
- Epigenomic Remodeling in Huntington's Disease-Master or Servant?Epigenomes · 2020Review
- DNA Methyltransferase 1 (DNMT1) Acts on Neurodegeneration by Modulating Proteostasis-Relevant Intracellular Processes.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epigenetic mechanisms of gene regulation, including DNA methylation and histone modifications, call increasing attention in the context of development and human health. Thereby, interactions between DNA methylating enzymes and histone modifications tremendously multiply the spectrum of potential regulatory functions. Epigenetic networks are critically involved in the establishment and functionality of neuronal circuits that are composed of gamma-aminobutyric acid (GABA)-positive inhibitory interneurons and excitatory principal neurons in the cerebral cortex. We recently reported a crucial role of the DNA methyltransferase 1 (DNMT1) during the migration of immature POA-derived cortical interneurons by promoting the migratory morphology through repression of Pak6. However, the DNMT1-dependent regulation of Pak6 expression appeared to occur independently of direct DNA methylation. Here, we show that in addition to its DNA methylating activity, DNMT1 can act on gene transcription by modulating permissive H3K4 and repressive H3K27 trimethylation in developing inhibitory interneurons, similar to what was found in other cell types. In particular, the transcriptional control of Pak6, interactions of DNMT1 with the Polycomb-repressor complex 2 (PCR2) core enzyme EZH2, mediating repressive H3K27 trimethylations at regulatory regions of the Pak6 gene locus. Similar to what was observed upon Dnmt1 depletion, inhibition of EZH2 caused elevated Pak6 expression levels accompanied by increased morphological complexity, which was rescued by siRNA-mediated downregulation of Pak6 expression. Together, our data emphasise the relevance of DNMT1-dependent crosstalk with histone tail methylation for transcriptional control of genes like Pak6 required for proper cortical interneuron migration.
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