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PLoS Genet. 2015 Oct 6;11(10):e1005555. doi: 10.1371/journal.pgen.1005555. eCollection 2015 Oct.

Chromatin-Remodelling Complex NURF Is Essential for Differentiation of Adult Melanocyte Stem Cells.

Author information

1
Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France; Beaston Institute for Cancer Research, Glasgow, United Kingdom.
2
Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France.
3
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
4
Institut Curie CNRS UMR3347, INSERM U1021, Bat 110, Orsay, France.
5
Institut Curie CNRS UMR3347, INSERM U1021, Bat 110, Orsay, France; Equipes labélisées Ligue Contre le Cancer, Orsay and Strasbourg, France.
6
Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France; Equipes labélisées Ligue Contre le Cancer, Orsay and Strasbourg, France.

Abstract

MIcrophthalmia-associated Transcription Factor (MITF) regulates melanocyte and melanoma physiology. We show that MITF associates the NURF chromatin-remodelling factor in melanoma cells. ShRNA-mediated silencing of the NURF subunit BPTF revealed its essential role in several melanoma cell lines and in untransformed melanocytes in vitro. Comparative RNA-seq shows that MITF and BPTF co-regulate overlapping gene expression programs in cell lines in vitro. Somatic and specific inactivation of Bptf in developing murine melanoblasts in vivo shows that Bptf regulates their proliferation, migration and morphology. Once born, Bptf-mutant mice display premature greying where the second post-natal coat is white. This second coat is normally pigmented by differentiated melanocytes derived from the adult melanocyte stem cell (MSC) population that is stimulated to proliferate and differentiate at anagen. An MSC population is established and maintained throughout the life of the Bptf-mutant mice, but these MSCs are abnormal and at anagen, give rise to reduced numbers of transient amplifying cells (TACs) that do not express melanocyte markers and fail to differentiate into mature melanin producing melanocytes. MSCs display a transcriptionally repressed chromatin state and Bptf is essential for reactivation of the melanocyte gene expression program at anagen, the subsequent normal proliferation of TACs and their differentiation into mature melanocytes.

PMID:
26440048
PMCID:
PMC4595011
DOI:
10.1371/journal.pgen.1005555
[Indexed for MEDLINE]
Free PMC Article

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