Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

59 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Recurrent amplifications of the histone methyltransferase SETDB1 in melanoma

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Richard Young

PROVIDER: E-GEOD-36579 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset

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. ChIP was performed from short-term cultures of WM262 and WM451Lu cells.

2011-03-25 | E-GEOD-28170 | biostudies-arrayexpress

ChIP-Seq of H3K79me2 in Mouse Embryonic Fibroblasts

Project description:H3K79 dimethylation is a mark of transcriptional elongation. To gain insight into the set of genes actively transcribed in MEFs, chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq) was performed to determine the presence of H3K79me2 across the genome. DNA was enriched by chromatin immunoprecipitation (ChIP) and analyzed by Solexa sequencing. ChIP was performed using an antibody against H3K79me2.

2010-06-15 | E-GEOD-22268 | biostudies-arrayexpress

ChIP-Seq of Pol2 in Mouse Embryonic Fibroblasts

Project description:RNA Polymerase II is the enzyme responsible for active transcription. To gain insight into the genes occupied by RNA Polymerase II and actively transcribed in MEFS, chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq) was performed to determine the genome-wide binding targets of RNA Pol2. DNA was enriched by chromatin immunoprecipitation (ChIP) and analyzed by Solexa sequencing. ChIP was performed using an antibody against RNA Polymerase II.

2010-06-15 | E-GEOD-22302 | biostudies-arrayexpress

ChIP-Seq of TBP in Mouse Embryonic Stem Cells

Project description:The TATA binding protein (TBP) is a transcription factor that binds specifically to a DNA sequence called the TATA box upstream of the transcription start site. To gain insight into the genes occupied by TBP, chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq) was performed to determine the genome-wide binding targets. DNA was enriched by chromatin immunoprecipitation (ChIP) and analyzed by Solexa sequencing. ChIP was performed using an antibody against TBP.

2010-06-15 | E-GEOD-22303 | biostudies-arrayexpress

Whole Cell Extract for Mouse Embryonic Fibroblasts

Project description:Mouse embryonic fibroblasts (MEFs) are an example of an early differentiated cell type. The whole cell extract was prepared in order to have background information for additional ChIP-Seq experiments in MEFs. The WCE data is a useful dataset that can be used as a background for many different analysis purposes. MEFs were sonicated, DNA was purified and prepared for solexa sequencing.

2010-06-15 | E-GEOD-22320 | biostudies-arrayexpress

Enhancer Invasion and Transcriptional Amplification in Tumor Cells with Elevated c-Myc

Project description:Excessive expression of c-Myc occurs frequently in human cancers, where high levels are associated with tumor aggression and poor clinical outcome, but the effect of high levels of c-Myc on global gene regulation is poorly understood. We report here that in tumor cells expressing high levels of c-Myc, the transcription factor binds to E-box sequences in the core promoters of most actively transcribed genes and, unexpectedly, the enhancers of these active genes. The predominant effect of increasing c-Myc levels at both proximal and distal promoter elements is to produce higher levels of transcription at existing active genes by promoting RNA polymerase II elongation, as opposed to stimulating transcription of novel target genes. Our results argue that c-Myc overexpression drives increased transcription of growth-promoting genes, and does so by amplifying the levels of transcripts associated with the entire gene expression program of the cancer cell. Thus, excess c-Myc functions to elicit the transcriptional amplification of existing active genes through the invasion of enhancers across the cancer cell genome, thereby reducing the rate-limiting constraints required for continuous tumor growth and proliferation. ChIP-Seq of multiple factors and histone modifications in a variety of human tumor cell lines

2012-04-04 | E-GEOD-36354 | biostudies-arrayexpress

Transcription factor binding in human embryonic stem cells

Project description:Cohesin interacts with Mediator to link the enhancers and core promoters of actively transcribed genes bound by RNA polymerase II. Activin signaling directs human embryonic stem cells to differentiate into endoderm. ChIP-seq was performed to determine the gene targets of these factors in human embryonic stem cells. Human ES cells were grown without feeders using mTESR1. ChIP-seq was performed against RNA Pol2, Cohesin subunits (Smc1 and Smc3) and IgG for cells grown in mTESR1. Cells were differentiated into endoderm after resting for 24 hours in RMPI-B27 (0hr), and then treating with 50 ng/ml Activin A for two hours (2hr) and 48 hours (48hr). DNA was enriched by chromatin immunoprecipitation (ChIP) and analyzed by Solexa sequencing.

2012-03-17 | E-GEOD-36578 | biostudies-arrayexpress

ChIP-Seq data for histone marks in mouse embryonic fibroblasts

Project description:The conversion of mouse embryonic fibroblasts (MEFs) to induced pluripotent stem cells (iPS) by forced expression of Oct4, Sox2 and Klf4 is among the earliest demonstrations of reprogramming to a pluripotent state by forced expression of transcription factors. To gain insights into the chromatin state of genes required for reprogramming, we profiled H3K4me3, H3K27me3 and H3K9me3. DNA was enriched by chromatin immunoprecipitation (ChIP) and analyzed by Solexa sequencing. ChIP was performed using an antibody against H3K4me3, H3K27me3 and H3K9me3.

2011-01-19 | E-GEOD-26657 | biostudies-arrayexpress

ChIP-seq of chromatin modifications and factors associated with transcriptionally active regions of the genome in mES cells

Project description:Post-translational modification of histones are coupled to transcription where certain modifications are indicative of an active or inactive region of the genome. Additionally, protein complexes can regulate the placement of nucleosomes across the genome and this influences the ability of DNA-binding proteins to interact with regions of the genome. The datasets presented here are ChIP-seq datasets for chromatin modifications associated with active or poised genes (H2Bub, H3K9,K14Ac and H3K4me3). Brg1 is a subunit of the SWI/SNF chromatin remodeling complex. An antibody specific to the chromatin modification or indicated factor was used to enrich for DNA fragments in murine embryonic stem cells. DNA was purified and prepared for Illumina/Solexa sequencing following their standard protocol.

2012-03-17 | E-GEOD-36561 | biostudies-arrayexpress

Recurrent amplifications of the histone methyltransferase SETDB1 in melanoma

2012-03-17 | GSE36579 | GEO