Lineage-Specific Transcriptional Regulation of DICER by MITF in Melanocytes | Zendy

Carmit Levy | Zendy; Mehdi Khaled | Zendy; Kathleen C. Robinson | Zendy; Rosa A. Veguilla | Zendy; Po-Hao Chen | Zendy; Satoru Yokoyama | Zendy; Eiichi Makino | Zendy; Jun Lü | Zendy; Lionel Larue | Zendy; Friedrich Beermann | Zendy; Lynda Chin | Zendy; Marcus Bosenberg | Zendy; Jun S. Song | Zendy; David E. Fisher | Zendy

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Lineage-Specific Transcriptional Regulation of DICER by MITF in Melanocytes

Author(s) -

Carmit Levy,

Mehdi Khaled,

Kathleen C. Robinson,

Rosa A. Veguilla,

Po-Hao Chen,

Satoru Yokoyama,

Eiichi Makino,

Jun Lü,

Lionel Larue,

Friedrich Beermann,

Lynda Chin,

Marcus Bosenberg,

Jun S. Song,

David E. Fisher

Publication year - 2010

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2010.05.004

Subject(s) - biology , microphthalmia associated transcription factor , dicer , lineage (genetic) , genetics , microbiology and biotechnology , evolutionary biology , transcription factor , gene , rna interference , rna

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.

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