title: Lineage-specific transcriptional regulation of DICER by MITF in melanocytes.
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.
authors.affiliation: Department of Dermatology, Cutaneous Biology Research Center, Mass. General Hospital, Harvard Medical School, MA 02115, USA.
authors.forename: Carmit
authors.initials: C
authors.lastname: Levy
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khaled
authors.forename: Kathleen C
authors.initials: KC
authors.lastname: Robinson
authors.forename: Rosa A
authors.initials: RA
authors.lastname: Veguilla
authors.forename: Po-Hao
authors.initials: PH
authors.lastname: Chen
authors.forename: Satoru
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Eiichi
authors.initials: E
authors.lastname: Makino
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Lionel
authors.initials: L
authors.lastname: Larue
authors.forename: Friedrich
authors.initials: F
authors.lastname: Beermann
authors.forename: Lynda
authors.initials: L
authors.lastname: Chin
authors.forename: Marcus
authors.initials: M
authors.lastname: Bosenberg
authors.forename: Jun S
authors.initials: JS
authors.lastname: Song
authors.forename: David E
authors.initials: DE
authors.lastname: Fisher
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D000078404:Epidermal Cells; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D018859:Hair Follicle / Q000378:metabolism; D006801:Humans; D008544:Melanocytes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism; D051739:Microphthalmia-Associated Transcription Factor / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C497234:MITF protein, human; D008565:Membrane Proteins; D035683:MicroRNAs; D051739:Microphthalmia-Associated Transcription Factor; D011518:Proto-Oncogene Proteins; D043244:Ribonuclease III