Cited by 499Neurogenesis and neuroplasticity mechanismsMicroRNA in disease regulationEpigenetics and DNA Methylation

Cross talk between microRNA and epigenetic regulation in adult neurogenesis

Open access
Szulwach, Keith E., Li, Xuekun, Smrt, Richard D., Li, Yujing, Luo, Yuping, Lin, Li, Santistevan, Nicholas J., Li, Wendi +2 more·2010·Journal of Cell Biology

Abstract

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 and is highly expressed at synapses in the cortex and hippocampus.

    “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”

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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
Published
2010-04-05
Volume
189
Issue
1
Pages
127-141
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
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
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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