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Lineage-specific transcriptional regulation of DICER by MITF in melanocytes.

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.

Pubmed ID: 20550935

Authors

  • Levy C
  • Khaled M
  • Robinson KC
  • Veguilla RA
  • Chen PH
  • Yokoyama S
  • Makino E
  • Lu J
  • Larue L
  • Beermann F
  • Chin L
  • Bosenberg M
  • Song JS
  • Fisher DE

Journal

Cell

Publication Data

June 11, 2010

Associated Grants

  • Agency: NIAMS NIH HHS, Id: R01 AR043369
  • Agency: NIAMS NIH HHS, Id: R01 AR043369-14
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Cell Differentiation
  • Cell Survival
  • Cells, Cultured
  • Epidermis
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Hair Follicle
  • Humans
  • Melanocytes
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs
  • Microphthalmia-Associated Transcription Factor
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins
  • Ribonuclease III
  • Transcription, Genetic
  • Up-Regulation