Inhibition of Ehmt2 promotes histone deacetylation-mediated neuronal differentiation of neural stem cells
| Autor: | Chen, Yen-Po, 陳彥博 |
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| Rok vydání: | 2011 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 99 Chromatin and epigenetic modifications play a central role in maintaining the gene expression programs that are important for both self-renewal and cell commitment. Recent research indicates that epigenetic modification may be integral to the cell fate commitment of neural stem cells. However, the molecules that are involved in this mechanism are not fully elucidated. Here we isolate mouse neuron stem cell (mNSC) from mouse embryonic brain (E11.5) and exposed mouse NSCs in vitro to HDAC inhibitors, valproic acid and sodium butyrate and a histone methyltransferase EHMT2 (G9a) inhibitor, BIX-01294, respectively, and analyzed their effects on mNSC differentiation. Both HDAC inhibitors and BIX-01294 enhance neuronal differentiation of mNSC which were characterized by increased elongation of neurites and increased expression of neuronal genes including Tuj1, Nfm and neuroD1. Expression of the synaptic proteins Synapsin and Synaptophysin which regulate release of neurotransmitter was increased in mNSC treated with valproic acid and is further increased in mNSC co-treated with valproic and BIX-01294. By delivering a HDAC inhibitor Suberoylanilide hydroxamic acid (SAHA) or BIX-01294 intraperitoneally in to adult mice, we show that expression of the young neuron marker doublecortin is significantly increased in the subventricular zone of lateral ventricle. Our results suggest that chromatin is dynamically remodeled during neurogenesis, and that di-methylation of histone H3 by Ehmt2 is associated with NSC self-renew in vitro and in vivo. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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