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Cross talk between microRNA and epigenetic regulation in adult neurogenesis
Open accessAbstract
Both microRNAs (miRNAs) and epigenetic regulation have important functions in stem cell biology, although the interactions between these two pathways are not well understood. Here, we show that MeCP2, a DNA methyl-CpG–binding protein, can epigenetically regulate specific miRNAs in adult neural stem cells (aNSCs). MeCP2-mediated epigenetic regulation of one such miRNA, miR-137, involves coregulation by Sox2, a core transcription factor in stem cells. miR-137 modulates the proliferation and differentiation of aNSCs in vitro and in vivo. Overexpression of miR-137 promotes the proliferation of aNSCs, whereas a reduction of miR-137 enhances aNSC differentiation. We further show that miR-137 post-transcriptionally represses the expression of Ezh2, a histone methyltransferase and Polycomb group (PcG) protein. The miR-137–mediated repression of Ezh2 feeds back to chromatin, resulting in a global decrease in histone H3 trimethyl lysine 27. Coexpression of Ezh2 can rescue phenotypes associated with miR-137 overexpression. These results demonstrate that cross talk between miRNA and epigenetic regulation contributes to the modulation of adult neurogenesis.
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“miR-137 is a key regulator of neuronal development with roles in neurogenesis and maturation 64,65 and is highly expressed at synapses in the cortex and hippocampus. 66”
From Genetic architectures of psychiatric disorders: the emerging picture and its implications (2012) · cites this paper as [65]
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Metadata
- Authors
- Szulwach, K. E., Li, X., Smrt, R. D., Li, Y., Luo, Y., Lin, L., Santistevan, N. J., Li, W., Zhao, X., & Jin, P.
- Affiliations
- Emory University (US)
- University of New Mexico (US)
- Department of Human Genetics 1 and 2
- Corresponding author
- Zhao, Xinyu
- Jin, Peng
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2010-04-05
- Volume
- 189
- Issue
- 1
- Pages
- 127-141
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2854370
- OpenAlex
- W2146997290
- Cited by
- 493
- References
- 69
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 28 · 2023: 13 · 2022: 22 · 2021: 31 · 2020: 13 · 2019: 28 · 2018: 22 · 2017: 34 · 2016: 43 · 2015: 45 · 2014: 55 · 2013: 43 · 2012: 48
- FWCI
- 14.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- Autism Speaks
- International Rett Syndrome Foundation
- National Institutes of Health
- National Institute on Aging (P50AG025688)
- National Institute of Mental Health (R01MH078972, MH078972, R56MH076090, MH080434, R01MH076090, MH076090, R01MH080434)
- National Institute of General Medical Sciences (T34GM008751)
- National Institute of Neurological Disorders and Stroke (NS051630, R01NS051630)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- microRNA, epigenetic regulation, adult neurogenesis, adult neural stem cells, MeCP2, miR-137, SOX2, EZH2, Polycomb group proteins, H3K27me3, DNA methylation, stem cell proliferation, stem cell differentiation, post-transcriptional regulation
- MeSH terms
- Enhancer of Zeste Homolog 2 Protein, Animals, Chromatin, Mice, Transgenic, Histone-Lysine N-Methyltransferase, Repressor Proteins, Stem Cells, MicroRNAs, Epigenesis, Genetic, Mice, Methyl-CpG-Binding Protein 2, Neurogenesis, Polycomb-Group Proteins, Polycomb Repressive Complex 2
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