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A positive feedback mechanism that regulates expression of miR-9 during neurogenesis.

التفاصيل البيبلوغرافية
العنوان: A positive feedback mechanism that regulates expression of miR-9 during neurogenesis.
المؤلفون: Jonathan L Davila, Loyal A Goff, Christopher L Ricupero, Cynthia Camarillo, Eileen N Oni, Mavis R Swerdel, Alana J Toro-Ramos, Jiali Li, Ronald P Hart
المصدر: PLoS ONE, Vol 9, Iss 4, p e94348 (2014)
بيانات النشر: Public Library of Science (PLoS), 2014.
سنة النشر: 2014
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
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.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: http://europepmc.org/articles/PMC3979806?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0094348
URL الوصول: https://doaj.org/article/f90389f00c9a4255b0bc206995a5d554
رقم الأكسشن: edsdoj.f90389f00c9a4255b0bc206995a5d554
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0094348