| Literature DB >> 20550935 |
Carmit Levy1, Mehdi Khaled, Kathleen C Robinson, Rosa A Veguilla, Po-Hao Chen, Satoru Yokoyama, Eiichi Makino, Jun Lu, Lionel Larue, Friedrich Beermann, Lynda Chin, Marcus Bosenberg, Jun S Song, David E Fisher.
Abstract
DICER is a central regulator of microRNA maturation. However, little is known about mechanisms regulating its expression in development or disease. While profiling miRNA expression in differentiating melanocytes, two populations were observed: some upregulated at the pre-miRNA stage, and others upregulated as mature miRNAs (with stable pre-miRNA levels). Conversion of pre-miRNAs to fully processed miRNAs appeared to be dependent upon stimulation of DICER expression--an event found to occur via direct transcriptional targeting of DICER by the melanocyte master transcriptional regulator MITF. MITF binds and activates a conserved regulatory element upstream of DICER's transcriptional start site upon melanocyte differentiation. Targeted KO of DICER is lethal to melanocytes, at least partly via DICER-dependent processing of the pre-miRNA-17 approximately 92 cluster thus targeting BIM, a known proapoptotic regulator of melanocyte survival. These observations highlight a central mechanism underlying lineage-specific miRNA regulation which could exist for other cell types during development. Copyright 2010 Elsevier Inc. All rights reserved.Entities:
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Year: 2010 PMID： 20550935 PMCID： PMC2897150 DOI： 10.1016/j.cell.2010.05.004
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582