First Author | Levy C | Year | 2010 |
Journal | Cell | Volume | 141 |
Issue | 6 | Pages | 994-1005 |
PubMed ID | 20550935 | Mgi Jnum | J:167944 |
Mgi Id | MGI:4881388 | Doi | 10.1016/j.cell.2010.05.004 |
Citation | Levy C, et al. (2010) Lineage-specific transcriptional regulation of DICER by MITF in melanocytes. Cell 141(6):994-1005 |
abstractText | 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. |