MicroRNA miR-124 controls the choice between neuronal and astrocyte differentiation by fine-tuning Ezh2 expression
Polycomb group protein Ezh2 is a histone H3 Lys-27 histone methyltransferase orchestrating an extensive epigenetic regulatory program. Several nervous system-specific genes are known to be repressed by Ezh2 in stem cells and derepressed during neuronal differentiation. However, the molecular mechani...
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sg-ntu-dr.10356-1067352023-02-28T16:56:09Z MicroRNA miR-124 controls the choice between neuronal and astrocyte differentiation by fine-tuning Ezh2 expression Neo, Wen Hao Yap, Karen Lee, Suet Hoay Looi, Liang Sheng Khandelia, Piyush Neo, Sheng Xiong Makeyev, Eugene V. Su, I-hsin School of Biological Sciences DRNTU::Science::Biological sciences::Molecular biology Polycomb group protein Ezh2 is a histone H3 Lys-27 histone methyltransferase orchestrating an extensive epigenetic regulatory program. Several nervous system-specific genes are known to be repressed by Ezh2 in stem cells and derepressed during neuronal differentiation. However, the molecular mechanisms underlying this regulation remain poorly understood. Here we show that Ezh2 levels are dampened during neuronal differentiation by brain-enriched microRNA miR-124. Expression of miR-124 in a neuroblastoma cells line was sufficient to up-regulate a significant fraction of nervous system-specific Ezh2 target genes. On the other hand, naturally elevated expression of miR-124 in embryonic carcinoma cells undergoing neuronal differentiation correlated with down-regulation of Ezh2 levels. Importantly, overexpression of Ezh2 mRNA with a 3′-untranslated region (3′-UTR) lacking a functional miR-124 binding site, but not with the wild-type Ezh2 3′-UTR, hampered neuronal and promoted astrocyte-specific differentiation in P19 and embryonic mouse neural stem cells. Overall, our results uncover a molecular mechanism that allows miR-124 to balance the choice between alternative differentiation possibilities through fine-tuning the expression of a critical epigenetic regulator. NMRC (Natl Medical Research Council, S’pore) Published version 2015-02-26T07:45:13Z 2019-12-06T22:17:15Z 2015-02-26T07:45:13Z 2019-12-06T22:17:15Z 2014 2014 Journal Article Neo, W. H., Yap, K., Lee, S. H., Looi, L. S., Khandelia, P., Neo, S. X., et al. (2014). MicroRNA miR-124 controls the choice between neuronal and astrocyte differentiation by fine-tuning Ezh2 expression. Journal of biological chemistry, 289(30), 20788-20801. https://hdl.handle.net/10356/106735 http://hdl.handle.net/10220/25120 10.1074/jbc.M113.525493 24878960 en The journal of biological chemistry © 2014 by The American Society for Biochemistry and Molecular Biology, Inc. Creative Commons Attribution Unported License applies to Author Choice Articles. 15 p. application/pdf |
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DRNTU::Science::Biological sciences::Molecular biology Neo, Wen Hao Yap, Karen Lee, Suet Hoay Looi, Liang Sheng Khandelia, Piyush Neo, Sheng Xiong Makeyev, Eugene V. Su, I-hsin MicroRNA miR-124 controls the choice between neuronal and astrocyte differentiation by fine-tuning Ezh2 expression |
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Polycomb group protein Ezh2 is a histone H3 Lys-27 histone methyltransferase orchestrating an extensive epigenetic regulatory program. Several nervous system-specific genes are known to be repressed by Ezh2 in stem cells and derepressed during neuronal differentiation. However, the molecular mechanisms underlying this regulation remain poorly understood. Here we show that Ezh2 levels are dampened during neuronal differentiation by brain-enriched microRNA miR-124. Expression of miR-124 in a neuroblastoma cells line was sufficient to up-regulate a significant fraction of nervous system-specific Ezh2 target genes. On the other hand, naturally elevated expression of miR-124 in embryonic carcinoma cells undergoing neuronal differentiation correlated with down-regulation of Ezh2 levels. Importantly, overexpression of Ezh2 mRNA with a 3′-untranslated region (3′-UTR) lacking a functional miR-124 binding site, but not with the wild-type Ezh2 3′-UTR, hampered neuronal and promoted astrocyte-specific differentiation in P19 and embryonic mouse neural stem cells. Overall, our results uncover a molecular mechanism that allows miR-124 to balance the choice between alternative differentiation possibilities through fine-tuning the expression of a critical epigenetic regulator. |
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School of Biological Sciences |
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School of Biological Sciences Neo, Wen Hao Yap, Karen Lee, Suet Hoay Looi, Liang Sheng Khandelia, Piyush Neo, Sheng Xiong Makeyev, Eugene V. Su, I-hsin |
format |
Article |
author |
Neo, Wen Hao Yap, Karen Lee, Suet Hoay Looi, Liang Sheng Khandelia, Piyush Neo, Sheng Xiong Makeyev, Eugene V. Su, I-hsin |
author_sort |
Neo, Wen Hao |
title |
MicroRNA miR-124 controls the choice between neuronal and astrocyte differentiation by fine-tuning Ezh2 expression |
title_short |
MicroRNA miR-124 controls the choice between neuronal and astrocyte differentiation by fine-tuning Ezh2 expression |
title_full |
MicroRNA miR-124 controls the choice between neuronal and astrocyte differentiation by fine-tuning Ezh2 expression |
title_fullStr |
MicroRNA miR-124 controls the choice between neuronal and astrocyte differentiation by fine-tuning Ezh2 expression |
title_full_unstemmed |
MicroRNA miR-124 controls the choice between neuronal and astrocyte differentiation by fine-tuning Ezh2 expression |
title_sort |
microrna mir-124 controls the choice between neuronal and astrocyte differentiation by fine-tuning ezh2 expression |
publishDate |
2015 |
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https://hdl.handle.net/10356/106735 http://hdl.handle.net/10220/25120 |
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1759855588649467904 |