Chromatin-Remodelling Complex NURF Is Essential for Differentiation of Adult Melanocyte Stem Cells
Dana Koludrovic,Patrick Laurette,Thomas Strub,Céline Keime,Madeleine Le Coz,Sebastien Coassolo,Gabrielle Mengus,Lionel Larue,Irwin Davidson +8 more
TLDR
It is shown that MITF associates the NURF chromatin-remodelling factor in melanoma cells and shRNA-mediated silencing of the NurF subunit BPTF revealed its essential role in several melanoma cell lines and in untransformed melanocytes in vitro.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.read more
Citations
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MITF—the first 25 years
Colin R. Goding,Heinz Arnheiter +1 more
TL;DR: The current understanding of MITF's role and regulation in development and disease, as well as those of the MITF-related factors TFEB and TFE3, are presented, and key areas where the knowledge ofMITF regulation and function is limited are highlighted.
Journal ArticleDOI
ATP-dependent chromatin remodeling during mammalian development
TL;DR: The mechanisms by which chromatin remodelers function and highlights their specificities during mammalian cell differentiation and organogenesis are summarized.
Journal ArticleDOI
Epigenetics of malignant melanoma.
TL;DR: This work focuses on the most current evidence around the epigenetic mechanisms: DNA methylation and demethylation including 5-hydroxy-methylcytosine; histone post-translational modifications including variant histones; chromatin remodelling complexes and in particular the polycomb-repressive complex PRC2 and its histone methyltransferase subunit EZH2; and non-coding RNAs.
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SIRT6 haploinsufficiency induces BRAF V600E melanoma cell resistance to MAPK inhibitors via IGF signalling
Thomas Strub,Flávia G. Ghiraldini,Saul Carcamo,Man Li,Aleksandra Wroblewska,Rajendra Singh,Matthew S. Goldberg,Dan Hasson,Zichen Wang,Stuart J. Gallagher,Peter Hersey,Avi Ma'ayan,Georgina V. Long,Richard A. Scolyer,Richard A. Scolyer,Brian D. Brown,Bin Zheng,Emily Bernstein +17 more
TL;DR: This study has not only identified an epigenetic mechanism of drug resistance, but also provides insights into a combinatorial therapy that may overcome resistance to standard-of-care therapy for BRAFV600-mutant melanoma patients.
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MITF-High and MITF-Low Cells and a Novel Subpopulation Expressing Genes of Both Cell States Contribute to Intra- and Intertumoral Heterogeneity of Primary Melanoma.
Marie Ennen,Céline Keime,Giovanni Gambi,Alice Kieny,Sebastien Coassolo,Christelle Thibault-Carpentier,Fanny Margerin-Schaller,Guillaume Davidson,Constance Vagne,Dan Lipsker,Irwin Davidson +10 more
TL;DR: Although tumors comprised variable proportions of cells with theMITF-high and MITF-low gene expression signatures characteristic of melanoma cultures, primary tumors also comprised cells expressing markers of both signatures defining a novel cell state in tumors in vivo.
References
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Journal ArticleDOI
A PHD finger of NURF couples histone H3 lysine 4 trimethylation with chromatin remodelling
Joanna Wysocka,Tomek Swigut,Hua Xiao,Thomas A. Milne,So Yeon Kwon,Joseph Landry,Monika Kauer,Alan J. Tackett,Brian T. Chait,Paul Badenhorst,Carl Wu,C. David Allis +11 more
TL;DR: This work shows that a plant homeodomain (PHD) finger of nucleosome remodelling factor (NURF), an ISWI-containing ATP-dependent chromatin-remodelling complex, mediates a direct preferential association with H3K4me3 tails, and identifies a previously unknown function for the PHD finger as a highly specialized methyl-lysine-binding domain.
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Melanocyte biology and skin pigmentation
Jennifer Y. Lin,David E. Fisher +1 more
TL;DR: Pigmentation mutants in various species are highly informative about basic genetic and developmental pathways, and provide important clues to the processes of photoprotection, cancer predisposition and even human evolution.
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Molecular basis for site-specific read-out of histone H3K4me3 by the BPTF PHD finger of NURF
Haitao Li,Serge Ilin,Wooikoon Wang,Elizabeth M. Duncan,Joanna Wysocka,C. David Allis,Dinshaw J. Patel +6 more
TL;DR: The molecular basis for specific recognition of H3(1–15)K4me3 by a plant homeodomains (PHD) finger of human BPTF (bromodomain and PHD domain transcription factor) is demonstrated and key specificity-determining residues from binding studies are identified.
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Quantitative Interaction Proteomics and Genome-wide Profiling of Epigenetic Histone Marks and Their Readers
Michiel Vermeulen,H. Christian Eberl,Filomena Matarese,Hendrik Marks,Sergei Denissov,Falk Butter,Kenneth K. Lee,Jesper V. Olsen,Jesper V. Olsen,Anthony A. Hyman,Henk Stunnenberg,Matthias Mann +11 more
TL;DR: The authors' data reveal a highly adapted interplay between chromatin marks and their associated protein complexes, and reading specific trimethyl-lysine sites by specialized complexes appears to be a widespread mechanism to mediate gene expression.
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Bcl2 Regulation by the Melanocyte Master Regulator Mitf Modulates Lineage Survival and Melanoma Cell Viability
Gaël McGill,Martin A. Horstmann,Hans R. Widlund,Jinyan Du,Gabriela Motyckova,Emi K. Nishimura,Yi Ling Lin,Sridhar Ramaswamy,Sridhar Ramaswamy,William Avery,Han Fei Ding,Siobhán A. Jordan,Ian J. Jackson,Stanley J. Korsmeyer,Todd R. Golub,Todd R. Golub,David E. Fisher +16 more
TL;DR: Clinically, primary human melanoma expression microarrays revealed tight nearest neighbor linkage for MITF and BCL2, which helps explain the vital roles of both Mitf and Bcl2 in the melanocyte lineage and the well-known treatment resistance of melanoma.