title: Chromatin-Remodelling Complex NURF Is Essential for Differentiation of Adult Melanocyte Stem Cells.
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.
authors.affiliation: 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.
authors.forename: Dana
authors.initials: D
authors.lastname: Koludrovic
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Laurette
authors.affiliation: Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Strub
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Keime
authors.affiliation: Institut Curie CNRS UMR3347, INSERM U1021, Bat 110, Orsay, France.
authors.forename: Madeleine
authors.initials: M
authors.lastname: Le Coz
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Coassolo
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch, France.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Mengus
authors.affiliation: Institut Curie CNRS UMR3347, INSERM U1021, Bat 110, Orsay, France; Equipes labélisées Ligue Contre le Cancer, Orsay and Strasbourg, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Larue
authors.affiliation: 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.
authors.forename: Irwin
authors.initials: I
authors.lastname: Davidson
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018859:Hair Follicle; D008544:Melanocytes / Q000378:metabolism; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D059630:Mesenchymal Stem Cells; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000092468:Bromodomain Containing Proteins
chemical_list: D034961:Antigens, Nuclear; D051739:Microphthalmia-Associated Transcription Factor; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; C497235:Mitf protein, mouse; C406238:fetal Alzheimer antigen; D000092468:Bromodomain Containing Proteins