|
| Status |
Public on Mar 25, 2011 |
| Title |
The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
The most common mutation in human melanoma, BRAF(V600E), activates the serine/threonine kinase BRAF and causes excessive activity in the mitogen-activated protein kinase pathway. BRAF(V600E) mutations are also present in benign melanocytic naevi, highlighting the importance of additional genetic alterations in the genesis of malignant tumours. Such changes include recurrent copy number variations that result in the amplification of oncogenes. For certain amplifications, the large number of genes in the interval has precluded an understanding of the cooperating oncogenic events. Here we have used a zebrafish melanoma model to test genes in a recurrently amplified region of chromosome 1 for the ability to cooperate with BRAF(V600E) and accelerate melanoma. SETDB1, an enzyme that methylates histone H3 on lysine 9 (H3K9), was found to accelerate melanoma formation significantly in zebrafish. Chromatin immunoprecipitation coupled with massively parallel DNA sequencing and gene expression analyses uncovered genes, including HOX genes, that are transcriptionally dysregulated in response to increased levels of SETDB1. Our studies establish SETDB1 as an oncogene in melanoma and underscore the role of chromatin factors in regulating tumorigenesis.
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| |
|
| Overall design |
ChIP was performed from short-term cultures of WM262 and WM451Lu cells.
|
| |
|
| Contributor(s) |
Bilodeau S, Young RA |
| Citation(s) |
21430779 |
| |
| Submission date |
Mar 24, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Richard A Young |
| E-mail(s) |
young_computation@wi.mit.edu
|
| Phone |
617-258-5219
|
| Organization name |
Whitehead Institute for Biomedical Research
|
| Lab |
Young Lab
|
| Street address |
9 Cambridge Center
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
|
| Samples (5)
|
| GSM697625 |
ChIP-Seq for SetDB1 in WM262 melanoma cells |
| GSM697626 |
ChIP-Seq for SetDB1 in Wm451-lu melanoma cells |
| GSM697627 |
ChIP-Seq for H3K9me3 in Wm451-lu melanoma cells |
| GSM697628 |
ChIP-Seq for H3K9me3 in WM262 melanoma cells |
| GSM697629 |
ChIP-Seq for MCAF1 in WM262 melanoma cells |
|
| This SubSeries is part of SuperSeries: |
| GSE26372 |
Expression analysis of melanoma harvested after GFP or SETDB1 expression |
|
| Relations |
| BioProject |
PRJNA143143 |
| SRA |
SRP013164 |
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