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Status |
Public on Apr 17, 2019 |
Title |
Chromatin remodellers Brg1 and Bptf are required for normal gene expression and progression of oncogenic Braf-driven mouse melanoma [ChIP-seq] |
Organism |
Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
Somatic oncogenic mutation of BRAF coupled with inactivation of PTEN constitute a frequent combination of genomic alterations driving development of human melanoma. Mice genetically engineered to conditionally express oncogenic BrafV600E and inactivate Pten in melanocytes following tamoxifen treatment rapidly develop melanoma. While early stage melanomas comprised melanin-pigmented Mitf and Dct-expressing cells, expression of these and other melanocyte identity genes was lost in later stage tumours that showed histological and molecular characteristics of de-differentiated neural crest type cells. Melanocyte identity genes displayed loss of active chromatin marks and RNA polymerase II and gain of heterochromatin marks indicating epigenetic reprogramming during tumour progression. Nevertheless, late stage tumour cells grown in culture re-expressed Mitf and melanocyte markers and Mitf together with Sox10 co-regulated a large number of genes essential for their growth. In this melanoma model, somatic inactivation that the catalytic Brg1 (Smarca4) subunit of the SWI/SNF complex and the scaffolding Bptf subunit of the NuRF delayed tumour formation and deregulated large and overlapping gene expression programs essential for normal tumour cell growth. Moreover, we show that Brg1 and Bptf co-regulated many genes together with Mitf and Sox10. Together these transcription factors and chromatin remodelling complexes orchestrate essential gene expression programs in mouse melanoma cells
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Overall design |
4 samples corresponding to genomic occupancy profiling of PolII, epigenetic landscape of H3K27me3 and H3K27ac and fixed sonicated genomic DNA input from mouse melanoma tumors.
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Contributor(s) |
Laurette P, Davidson I, Coassolo S |
Citation(s) |
31065107 |
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Submission date |
Jul 09, 2017 |
Last update date |
Jul 25, 2021 |
Contact name |
Irwin Davidson |
E-mail(s) |
irwin67000@gmail.com
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Organization name |
IGBMC
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Street address |
1 Rue Laurent Fries
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City |
Strasbourg |
ZIP/Postal code |
67404 |
Country |
France |
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Platforms (1) |
GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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Samples (4)
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This SubSeries is part of SuperSeries: |
GSE129621 |
Chromatin remodellers Brg1 and Bptf are required for normal gene expression and progression of oncogenic Braf-driven mouse melanoma |
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Relations |
BioProject |
PRJNA393583 |
SRA |
SRP111416 |