A Positive Feedback Mechanism That Regulates Expression of miR-9 during Neurogenesis
| العنوان: | A Positive Feedback Mechanism That Regulates Expression of miR-9 during Neurogenesis |
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| المؤلفون: | Mavis R. Swerdel, Jonathan Davila, Alana J. Toro-Ramos, Loyal A. Goff, Jiali Li, Cynthia Camarillo, Eileen N. Oni, Christopher L. Ricupero, Ronald P. Hart |
| المصدر: | PLoS ONE PLoS ONE, Vol 9, Iss 4, p e94348 (2014) |
| بيانات النشر: | Public Library of Science (PLoS), 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Transcription, Genetic, Cellular differentiation, Regulator, lcsh:Medicine, Cell Fate Determination, 0302 clinical medicine, Neural Stem Cells, Animal Cells, lcsh:Science, Promoter Regions, Genetic, 3' Untranslated Regions, Cell Line, Transformed, Feedback, Physiological, Neurons, Genetics, 0303 health sciences, Gene knockdown, Multidisciplinary, MEF2 Transcription Factors, Stem Cells, Neurogenesis, Gene Expression Regulation, Developmental, Cell Differentiation, Cell biology, Cellular Types, Protein Binding, Research Article, Mef2, Biology, Histone Deacetylases, 03 medical and health sciences, Developmental Neuroscience, microRNA, Animals, RNA, Messenger, Transcription factor, 030304 developmental biology, Binding Sites, Base Sequence, lcsh:R, Biology and Life Sciences, Cell Biology, HDAC4, Rats, MicroRNAs, lcsh:Q, 030217 neurology & neurosurgery, Developmental Biology, Neuroscience |
| الوصف: | 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. |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1a399eb7bc02541bfe7a4fb2be28331f https://doi.org/10.1371/journal.pone.0094348 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....1a399eb7bc02541bfe7a4fb2be28331f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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