Dnmt3a-Dependent Nonpromoter DNA Methylation Facilitates Transcription of Neurogenic Genes
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Location, Location, Location: The genome receives epigenetic marks throughout development that regulate the activity of multiple genes. One such mark is methylation, which usually represses gene transcription. Methylation has generally been studied in the promoters of genes, where many regulatory signals coordinate to control the expression of the gene. Studying neural stem cells from mice, Wu et al. (p. 444 ) now show that DNA methylation can be a double-edged sword. Although methylation of DNA sequences in promoters tends to be repressive, methylation of DNA sequences beyond the promoters can actually promote gene expression. Analysis of the methyltransferase Dnmt3a in mouse neural stem cells revealed that methylations around neurogenic genes—but outside their promoters—maintained the activity of these genes.
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Methylation of non-proximal promoters dependent on DNMT3a enhances expression of a large cohort of neurogenic genes.
“One study showed that the methylation of non-proximal promoters, which is dependent on DNMT3a, enhances the expression of a large cohort of neurogenic genes.54”
From Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential (2023) · cites this paper as [54]
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- Authors
- Wu, H., Coskun, V., Tao, J., Xie, W., Ge, W., Yoshikawa, K., Li, E., Zhang, Y., & Sun, Y. E.
- Affiliations
- University of California, Los Angeles (US)
- Institute for Protein Research, The University of Osaka (JP)
- Novartis Institutes for Biomedical Research, Cambridge, MA 02139, USA.
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Wu, Hao
- Sun, Yi Eve
- Venue
- Science
- Published
- 2010-07-23
- Volume
- 329
- Issue
- 5990
- Pages
- 444-448
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3539760
- OpenAlex
- W1968717432
- Cited by
- 604
- References
- 4
- Citations by year
- 2026: 6 · 2025: 21 · 2024: 32 · 2023: 16 · 2022: 28 · 2021: 36 · 2020: 33 · 2019: 41 · 2018: 38 · 2017: 41 · 2016: 42 · 2015: 39 · 2014: 66 · 2013: 61 · 2012: 48
- FWCI
- 21.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DNMT3A, neural stem cells, neurogenesis, Polycomb repression, intergenic regions, gene body methylation, transcriptional regulation, active chromatin, lineage restriction
- MeSH terms
- DNA Methyltransferase 3A, Animals, Binding Sites, Brain, DNA (Cytosine-5-)-Methyltransferases, Histones, Nervous System, Neuroglia, Neurons, Promoter Regions, Genetic, Repressor Proteins, Stem Cells, Transcription, Genetic, Genome, Mice, Knockout, Gene Expression Regulation, Developmental, DNA Methylation, Gene Expression Profiling, DNA, Intergenic, Chromatin Immunoprecipitation, Mice, Neurogenesis, Polycomb-Group Proteins
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