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Expression analysis of melanoma harvested from GFP versus SETDB1 transgenic zebrafish (Danio rerio)

ABSTRACT: Investigation of expression differences between melanomas harvested from MiniCoopR-GFP versus MiniCoopR-SETDB1 transgenic zebrafish.

ORGANISM(S): Danio rerio

PROVIDER: GSE21505 | GEO | 2011/01/07

SECONDARY ACCESSION(S): PRJNA141703

REPOSITORIES: GEO

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Expression analysis of melanoma harvested from GFP versus SETDB1 transgenic zebrafish (Danio rerio)

Project description:Investigation of expression differences between melanomas harvested from MiniCoopR-GFP versus MiniCoopR-SETDB1 transgenic zebrafish. An eight-chip study using total RNA prepared from four distinct melanomas from zebrafish injected with MiniCoopR-GFP (control) transposon and four distinct melanomas from zebrafish injected with MiniCoopR-SETDB1 transposon. Injected animals carried a p53 loss-of-function mutation, a mutation in nacre, and an mitf:BRAF-V600E transgene. Each chip measures the expression level of 32,292 genes.

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Expression analysis of melanoma harvested after GFP or SETDB1 expression

Project description:This SuperSeries is composed of the following subset Series: GSE21505: Expression analysis of melanoma harvested from GFP versus SETDB1 transgenic zebrafish (Danio rerio) GSE26371: Expression analysis of human melanoma short-term culture WM451-Lu harvested after lentiviral infection with a GFP (control) or SETDB1 (experimental) viral vector Refer to individual Series

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Expression analysis of human melanoma short-term culture WM451-Lu harvested after lentiviral infection with a GFP (control) or SETDB1 (experimental) viral vector

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Expression analysis of human melanoma short-term culture WM451-Lu harvested after lentiviral infection with a GFP (control) or SETDB1 (experimental) viral vector

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The histone methyltransferase SETDB1 contributes to melanoma tumorigenesis and serves as a new potential therapeutic target in BRAF/MEK inhibitor-resistant melanoma [ChIP-seq]

Project description:Histone modifications play a crucial role in the progression of various cancers. The histone methyltransferase SETDB1 catalyzes the addition of methyl groups to histone H3 at lysine 9. Here, we describe SETDB1 contribution to melanoma tumorigenesis. SETDB1 is highly amplified in melanoma cells and in patients’ tumors. Increased SETDB1 expression, which correlates with SETDB1 amplification, is associated with a more aggressive phenotype in in vitro and in vivo studies. SETDB1 implements its effects through the regulation of Thrombospondin 1. SETDB1’s SET-domain is essential to maintain its tumorigenic effects. SETDB1 inhibition reduces cell growth in melanomas resistant to targeted treatments. In essence, we support SETDB1 as a major driver of melanoma development, highlighting a role as potential future target for the treatment of this disease.

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Expression analysis of melanoma harvested after GFP or SETDB1 expression

Project description:This SuperSeries is composed of the SubSeries listed below.

2011-01-07 | GSE26372 | GEO

Expression analysis of human melanoma short-term culture WM451-Lu harvested after lentiviral infection with a GFP (control) or SETDB1 (experimental) viral vector

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Analyzing cold tolerance mechanism in transgenic zebrafish (Danio rerio).

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The histone methyltransferase SETDB1 contributes to melanoma tumorigenesis and serves as a new potential therapeutic target in BRAF/MEK inhibitor-resistant melanoma [SETDB1]

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Project description: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. DNA was enriched from short-term cultures of cells and chromatin immunoprecipitations (ChIPs) were analyzed by Solexa sequencing. ChIPs were performed using an antibody against SetDB1 in WM853.2. Whole cell extracts are provided for WM262, WM451Lu and WM853.2 cells.

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