Dnmt3a Regulates Global Gene Expression in Olfactory Sensory Neurons and Enables Odorant-Induced Transcription
Open accessAbstract
During differentiation, neurons exhibit a reorganization of DNA modification patterns across their genomes. The de novo DNA methyltransferase Dnmt3a is implicated in this process, but the effects of its absence have not been fully characterized in a purified neuronal population. To better understand how DNA modifications contribute to neuronal function, we performed a comprehensive analysis of the epigenetic and transcriptional landscapes of Dnmt3a-deficient mature olfactory sensory neurons (mOSNs), the primary sensory neurons of the olfactory epithelium. Dnmt3a is required for both 5-methylcytosine and 5-hydroxymethylcytosine patterning within accessible genomic regions, including hundreds of neurodevelopmental genes and neural enhancers. Loss of Dnmt3a results in the global disruption of gene expression via activation of silent genes and reduction of mOSN-expressed transcripts. Importantly, the DNA modification state and inducibility of odorant-activated genes are markedly impaired in Dnmt3a knockouts, suggesting a crucial role for this enzyme in establishing an epigenetic landscape compatible with neuronal plasticity.
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The de-enrichment of Ace2 and Tmprss2 in olfactory sensory neurons relative to whole olfactory mucosa was also observed in two other mouse RNA-Seq datasets.
“The de-enrichment of Ace2 and Tmprss2 in OSNs relative to WOM was also observed in two other mouse RNA-Seq datasets (47, 48) (Figure S4B).”
From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [48]
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- Authors
- Colquitt, B. M., Markenscoff-Papadimitriou, E., Duffié, R., & Lomvardas, S.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Lomvardas, Stavros
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2014-08
- Volume
- 83
- Issue
- 4
- Pages
- 823-838
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC4153871
- OpenAlex
- W2064451824
- Cited by
- 38
- References
- 55
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 3 · 2018: 8 · 2017: 3 · 2016: 7 · 2015: 2 · 2014: 1
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health (1dp2od006667-01)
- National Institute of Mental Health (R01MH091661)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- DNMT3A, de novo methylation, olfactory sensory neurons, 5-hydroxymethylcytosine, 5-methylcytosine, DNA methylation, gene expression regulation, epigenetic landscape, neuroplasticity, neurodevelopmental genes, olfactory epithelium
- MeSH terms
- DNA Methyltransferase 3A, Animals, Cells, Cultured, DNA (Cytosine-5-)-Methyltransferases, Gene Expression Regulation, Neuronal Plasticity, Smell, Olfactory Receptor Neurons, DNA Methylation, Mice, Olfactory Perception, Epigenomics
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