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PMID: 20550935 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Cell ·Vol. 141 ·No. 6 ·2010-06-11 ·Pages 994-1005

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

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.

MeSH Terms
Animals Apoptosis Regulatory Proteins/metabolism Bcl-2-Like Protein 11 Cell Differentiation Cell Survival Cells, Cultured Epidermal Cells Gene Expression Regulation Gene Knockdown Techniques Hair Follicle/metabolism Humans Melanocytes/metabolism Membrane Proteins/metabolism Mice Mice, Inbred C57BL MicroRNAs/metabolism Microphthalmia-Associated Transcription Factor/metabolism Promoter Regions, Genetic Proto-Oncogene Proteins/metabolism Ribonuclease III/metabolism Transcription, Genetic Up-Regulation
Chemicals
Apoptosis Regulatory Proteins BCL2L11 protein, human Bcl-2-Like Protein 11 Bcl2l11 protein, mouse MITF protein, human Membrane Proteins MicroRNAs Microphthalmia-Associated Transcription Factor Proto-Oncogene Proteins Ribonuclease III
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Levy Carmit
Department of Dermatology, Cutaneous Biology Research Center, Mass. General Hospital, Harvard Medical School, MA 02115, USA.
Khaled Mehdi
Robinson Kathleen C
Veguilla Rosa A
Chen Po-Hao
Yokoyama Satoru
Makino Eiichi
Lu Jun
Larue Lionel
Beermann Friedrich
Chin Lynda
Bosenberg Marcus
Song Jun S
Fisher David E
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2010.05.004
Published
2010-06-11
Pages
994-1005
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2897150
Subset
IM
Grants
NIAMS NIH HHS · R01 AR043369 · United States
NIAMS NIH HHS · R01 AR043369-14 · United States
Howard Hughes Medical Institute · United States
Databases
GEO
GSE21249
External Links
PubMed source DOI: 10.1016/j.cell.2010.05.004 PMC Full Text View journal details
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