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| Status |
Public on Feb 12, 2023 |
| Title |
NR2F2 ChIP-sequencing of melanoma cell lines |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Melanoma is a highly metastatic tumor type responsible of the large majority of the skin cancer-related deaths. Melanoma cells recapitulate the migratory and invasive nature of neural crest stem cells from which melanocytes arise. However, the mechanisms by which these developmental programs confer melanoma cells with more aggressive properties are not understood. Here we provide evidence for an epigenetically regulated developmental program that is aberrantly re-activated by melanoma cells to aid in the metastatic process. We reasoned that studying molecular changes occurring during the ontogeny of melanocytes from progenitor neural crest cells (NCC), and identifying developmental programs retained or re-gained by melanoma cells, could reveal crucial processes that modulate melanoma aggressiveness. Here we describe a novel mechanism that controls the activity of a transcriptional regulator of human neural crest, the Nuclear Receptor Subfamily 2 Group F, Member 2 (NR2F2). We find that highly localized DNA methylation acts as an on/off switch that controls the expression of a truncated NR2F2 isoform (NR2F2-Iso2) from an alternative transcription start site during NCC to melanocyte differentiation. We show that melanoma cells co-opt this developmental program by decreased DNA methylation and re-expression of NR2F2-Iso2 to promote melanoma metastasis. NR2F2-Iso2 regulates the transcriptional activity of the full length NR2F2 isoform 1 by impairing its binding to chromatin, which results in altered expression of NCC and differentiation genes. Our data demonstrate that epigenetic reactivation of NR2F2 isoform 2 promotes melanoma metastasis, which could be targeted for therapeutic purposes.
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| Overall design |
NR2F2-isoform 2 loss-of-function (shRNA) cellular models were generated in 4L melanoma cell line.
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| Contributor(s) |
Davalos V, Hernando E |
| Citation(s) |
37015919 |
| |
| Submission date |
Aug 11, 2017 |
| Last update date |
May 15, 2023 |
| Contact name |
Igor Dolgalev |
| Organization name |
NYU Grossman School of Medicine
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| Street address |
550 1st Ave
|
| City |
New York |
| State/province |
New York |
| ZIP/Postal code |
10016 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
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| Relations |
| BioProject |
PRJNA398020 |
| SRA |
SRP115284 |
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