...bone marrow mesenchymal stem cells via targeting zinc...

来自 : www.oalib.com/references/5870. 发布时间：2021-03-24

ABSTRACT: MiR-9, a neuron-specific miRNA, is an important regulator of neurogenesis. In this study we identify how miR-9 is regulated during early differentiation from a neural stem-like cell. We utilized two immortalized rat precursor clones, one committed to neurogenesis (L2.2) and another capable of producing both neurons and non-neuronal cells (L2.3), to reproducibly study early neurogenesis. Exogenous miR-9 is capable of increasing neurogenesis from L2.3 cells. Only one of three genomic loci capable of encoding miR-9 was regulated during neurogenesis and the promoter region of this locus contains sufficient functional elements to drive expression of a luciferase reporter in a developmentally regulated pattern. Furthermore, among a large number of potential regulatory sites encoded in this sequence, Mef2 stood out because of its known pro-neuronal role. Of four Mef2 paralogs, we found only Mef2C mRNA was regulated during neurogenesis. Removal of predicted Mef2 binding sites or knockdown of Mef2C expression reduced miR-9-2 promoter activity. Finally, the mRNA encoding the Mef2C binding partner HDAC4 was shown to be targeted by miR-9. Since HDAC4 protein could be co-immunoprecipitated with Mef2C protein or with genomic Mef2 binding sequences, we conclude that miR-9 regulation is mediated, at least in part, by Mef2C binding but that expressed miR-9 has the capacity to reduce inhibitory HDAC4, stabilizing its own expression in a positive feedback mechanism.
Han R, Kan Q, Sun Y, Wang S, Zhang G, et al. (2012) MiR-9 promotes the neural differentiation of mouse bone marrow mesenchymal stem cells via ...Han R, Kan Q, Sun Y, Wang S, Zhang G, et al. (2012) MiR-9 promotes the neural differentiation of mouse bone marrow mesenchymal stem cells via targeting zinc finger protein 521. Neurosci Lett 515: 147–152. doi: 10.1016/j.neulet.2012.03.032Han R, Kan Q, Sun Y, Wang S, Zhang G, et al. (2012) MiR-9 promotes the neural differentiation of mouse bone marrow mesenchymal stem cells via targeting zinc finger protein 521. Neurosci Lett 515: 147–152. doi: 10.1016/j.neulet.2012.03.032Han R, Kan Q, Sun Y, Wang S, Zhang G, et al. (2012) MiR