Lineage-specific transcriptional regulation of DICER by MITF in melanocytes

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

doi:10.1016/j.cell.2010.05.004

Lineage-specific transcriptional regulation of DICER by MITF in melanocytes

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

Genomic Medicine

Research output: Contribution to journal › Article › peer-review

103 Scopus citations

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∼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.

Original language	English (US)
Pages (from-to)	994-1005
Number of pages	12
Journal	Cell
Volume	141
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2010.05.004
State	Published - Jun 2010

Keywords

Cellbio
Devbio
RNA

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2010.05.004

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@article{68ae59cbe723426bb89676975563e7e0,

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∼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.",

keywords = "Cellbio, Devbio, RNA",

author = "Carmit Levy and Mehdi Khaled and Robinson, {Kathleen C.} and Veguilla, {Rosa A.} and Chen, {Po Hao} and Satoru Yokoyama and Eiichi Makino and Jun Lu and Lionel Larue and Friedrich Beermann and Lynda Chin and Marcus Bosenberg and Song, {Jun S.} and Fisher, {David E.}",

note = "Funding Information: The authors gratefully acknowledge help from Dr. Rod Bronson with mouse pathology; Dr. Carl Novina for useful discussions; Dr. Ian Jackson for Dct-LacZ transgenic mice; Dr. T. Kunisada for K14-SCF transgenic mice; Dr. Clifford J. Tabin for Dicer Floxed mice; Dr. Ruth Halaban for 501mel melanoma cells; Maja Janas, Ana Hernandez, Dr. Jacob Hanna, and members of the Fisher lab for help with numerous aspects of this work. JSS was supported in part by the Martin A. and Helen Chooljian Membership. D.E.F. gratefully acknowledges grant support from NIH, The Melanoma Research Alliance, The Doris Duke Charitable Foundation, The Adelson Medical Research Foundation, and the Israel-US Binational Science Foundation. ",

year = "2010",

month = jun,

doi = "10.1016/j.cell.2010.05.004",

language = "English (US)",

volume = "141",

pages = "994--1005",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "6",

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TY - JOUR

T1 - Lineage-specific transcriptional regulation of DICER by MITF in melanocytes

AU - Levy, Carmit

AU - Khaled, Mehdi

AU - Robinson, Kathleen C.

AU - Veguilla, Rosa A.

AU - Chen, Po Hao

AU - Yokoyama, Satoru

AU - Makino, Eiichi

AU - Lu, Jun

AU - Larue, Lionel

AU - Beermann, Friedrich

AU - Chin, Lynda

AU - Bosenberg, Marcus

AU - Song, Jun S.

AU - Fisher, David E.

N1 - Funding Information: The authors gratefully acknowledge help from Dr. Rod Bronson with mouse pathology; Dr. Carl Novina for useful discussions; Dr. Ian Jackson for Dct-LacZ transgenic mice; Dr. T. Kunisada for K14-SCF transgenic mice; Dr. Clifford J. Tabin for Dicer Floxed mice; Dr. Ruth Halaban for 501mel melanoma cells; Maja Janas, Ana Hernandez, Dr. Jacob Hanna, and members of the Fisher lab for help with numerous aspects of this work. JSS was supported in part by the Martin A. and Helen Chooljian Membership. D.E.F. gratefully acknowledges grant support from NIH, The Melanoma Research Alliance, The Doris Duke Charitable Foundation, The Adelson Medical Research Foundation, and the Israel-US Binational Science Foundation.

PY - 2010/6

Y1 - 2010/6

N2 - 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∼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.

AB - 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∼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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KW - Devbio

KW - RNA

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DO - 10.1016/j.cell.2010.05.004

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VL - 141

SP - 994

EP - 1005

JO - Cell

JF - Cell

IS - 6

ER -

Lineage-specific transcriptional regulation of DICER by MITF in melanocytes

Abstract

Keywords

ASJC Scopus subject areas

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