Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hijacking of stress response machinery by oncogenes in acute leukaemia [ChIP-seq]

ABSTRACT: HSF1 orchestrates the heat shock response pathway. This pathway is co-opted in cancer and provides critical stress relief from oncogenic stress. HSF1 has a diverse occupancy signature depending on the cell type. In this study, we performed HSF1 ChIP-seq analysis using the human T-ALL cell line CUTLL1 and P12. These results revealed the HSF1 chromatin binding signature in CUTLL1 and P12 cells. MYC is a driving oncogene in T-ALL. The non-oncogene addiction pathways that act downstream of this transcription factor to support anabolic pathways are not well-understood. For this reason, we performed MYC ChIP-seq analysis using the human T-ALL cell line CUTLL1. These results revealed that HSF1 and HSF1 targets are included in the MYC binding signature.

ORGANISM(S): Homo sapiens

PROVIDER: GSE90716 | GEO | 2018/03/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hijacking of stress response machinery by oncogenes in acute leukaemia [RNA-seq]

Project description:Our data demonstrate binding of NOTCH1 on the promoters of HSF1 and HSF1 targets. We performed RNA-seq upon control conditions, inhibition of the NOTCH1 pathway by gSI, HSF1 knockdown and combination of HSF1 knockdown and gSI treatment. Our results show that NOTCH1 regulates the expression of heat shock response genes. Moreover, combination of HSF1 downregulation and gSI treatment further decreased the expression of heat shock response genes compared to single treatments.

2018-03-20 | GSE90715 | GEO

Oncogenes hijack the stress response machinery in T cell acute lymphoblastic leukemia [GRO-Seq]

Project description:Oncogenes NOTCH1 and MYC directly regulate HSF1 and other critical proteins of the stress-response pathway in T-ALL. This GRO-Seq experiment demonstrates that release from NOTCH1 inhibition results in upregulation of HSF1 and other key HSPs.

2018-03-20 | GSE101803 | GEO

Enhancer hijacking activates GFI1 family oncogenes in medulloblastoma.

Project description:Medulloblastoma is a highly malignant paediatric brain tumour currently treated with a combination of surgery, radiation and chemotherapy, posing a considerable burden of toxicity to the developing child. Genomics has illuminated the extensive intertumoral heterogeneity of medulloblastoma, identifying four distinct molecular subgroups. Group 3 and group 4 subgroup medulloblastomas account for most paediatric cases; yet, oncogenic drivers for these subtypes remain largely unidentified. Here we describe a series of prevalent, highly disparate genomic structural variants, restricted to groups 3 and 4, resulting in specific and mutually exclusive activation of the growth factor independent 1 family proto-oncogenes, GFI1 and GFI1B. Somatic structural variants juxtapose GFI1 or GFI1B coding sequences proximal to active enhancer elements, including super-enhancers, instigating oncogenic activity. Our results, supported by evidence from mouse models, identify GFI1 and GFI1B as prominent medulloblastoma oncogenes and implicate 'enhancer hijacking' as an efficient mechanism driving oncogene activation in a childhood cancer.

| S-EPMC4201514 | biostudies-literature

Identification of novel candidate oncogenes in chromosomal region 17p11.2-p12 in human osteosarcoma

Project description:in 25% - 30% of all OS cases the chromosome region 17p11.2-p12 is aberrant. Using SNP array in conjunction with expression microarrays we try to identify genes which can be classified as oncogens or are in someway benificial to the survival of the tumor. To identify minimal significant amplified region(s) that is(are) aberrant in osteosarcoma tumorigenesis, with a special emphasis on but not limitied to chromosome region 17p11.2-p12

2013-04-15 | E-GEOD-32964 | biostudies-arrayexpress

Heat shock factor 1 specifically potentiates c-MYC-mediated transcription independently of the canonical heat-shock response

Project description:Despite its pivotal roles in biology, how the transcriptional activity of c-MYC is attuned quantitatively remain poorly defined. Here, we show that heat shock factor 1 (HSF1), the master transcriptional regulator of the heat-shock response, acts as a key modifier of the c-MYC-mediated transcription. HSF1 deficiency diminishes c-MYC DNA binding and dampens its transcriptional activity genome-widely. Mechanistically, c-MYC, MAX, and HSF1 assemble into a transcription factor complex on DNAs and, surprisingly, the DNA binding of HSF1 is dispensable. Instead, HSF1 physically recruits the histone acetyltransferase GCN5, thereby promoting histone acetylation and augmenting c-MYC transcriptional activity. Thus, our studies reveal that HSF1 specifically potentiates the c-MYC-mediated transcription, distinct from its role in the canonical heat-shock response. Importantly, this mechanism of action engenders two distinct c-MYC activation states, primary and advanced, which may be important to accommodate diverse physiological and pathological conditions.

2023-05-22 | GSE199462 | GEO

Epigenomic translocation of H3K4me3 broad domains over oncogenes following hijacking of super-enhancers.

Project description:Chromosomal translocations are important drivers of haematological malignancies whereby proto-oncogenes are activated by juxtaposition with enhancers, often called enhancer hijacking We analyzed the epigenomic consequences of rearrangements between the super-enhancers of the immunoglobulin heavy locus (IGH) and proto-oncogene CCND1 that are common in B cell malignancies. By integrating BLUEPRINT epigenomic data with DNA breakpoint detection, we characterized the normal chromatin landscape of the human IGH locus and its dynamics after pathological genomic rearrangement. We detected an H3K4me3 broad domain (BD) within the IGH locus of healthy B cells that was absent in samples with IGH-CCND1 translocations. The appearance of H3K4me3-BD over CCND1 in the latter was associated with overexpression and extensive chromatin accessibility of its gene body. We observed similar cancer-specific H3K4me3-BDs associated with hijacking of super-enhancers of other common oncogenes in B cell (MAF, MYC, and FGFR3/NSD2) and T cell malignancies (LMO2, TLX3, and TAL1). Our analysis suggests that H3K4me3-BDs can be created by super-enhancers and supports the new concept of epigenomic translocation, in which the relocation of H3K4me3-BDs from cell identity genes to oncogenes accompanies the translocation of super-enhancers.

| S-EPMC9341503 | biostudies-literature

Function of plant oncogenes(1)

Project description:The rolB plant oncogene exerts its oncogenic properties by modulating the abundance of chaperones

2018-02-09 | PXD005889 | Pride

Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers

Project description:Chromatin regulators have become highly attractive targets for cancer therapy, yet many of these regulators are expressed in a broad range of healthy cells and contribute generally to gene expression. An important conundrum has thus emerged: how can inhibition of a general regulator of gene expression produce selective effects at specific oncogenes? Here we investigate how inhibition of the transcriptional coactivator BRD4 (Bromodomain containing 4) leads to selective inhibition of disease-critical oncogenes in a highly malignant blood cancer, multiple myeloma (MM). We found that BRD4 generally occupies the promoter elements of active genes together with the Mediator coactivator, but remarkably high levels of these two coactivator proteins were associated with a small set of exceptionally large enhancers. These super-enhancers are associated with genes that feature prominently in MM biology, including the MYC oncogene. Treatment of MM tumor cells with the BET-bromodomain inhibitor JQ1 led to preferential loss of BRD4 at super-enhancers and consequent transcription elongation defects that preferentially impact genes with super-enhancers, including the c-MYC oncogene. Super-enhancers were found at key oncogenic drivers in many other tumor cells. Thus, super-enhancers can regulate oncogenic drivers in tumor cells, which in some cells can be preferentially disrupted by BRD4 inhibition, which in turn contributes to the selective transcriptional effects observed at these oncogenes. These observations have implications for the discovery of novel cancer therapeutics directed at components of super-enhancers in diverse tumor types. ChIP-Seq for chromatin regulators and RNA Polymerase II in multiple myeloma, glioblastoma multiforme, and small cell lung cancer

2013-01-02 | E-GEOD-42355 | biostudies-arrayexpress

Homo sapiens

Project description:Oncogene Signature Dataset

| PRJNA92983 | ENA

Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers [Affymetrix]

Project description:Chromatin regulators have become highly attractive targets for cancer therapy, yet many of these regulators are expressed in a broad range of healthy cells and contribute generally to gene expression. An important conundrum has thus emerged: how can inhibition of a general regulator of gene expression produce selective effects at specific oncogenes? Here we investigate how inhibition of the transcriptional coactivator BRD4 (Bromodomain containing 4) leads to selective inhibition of disease-critical oncogenes in a highly malignant blood cancer, multiple myeloma (MM). We found that BRD4 generally occupies the promoter elements of active genes together with the Mediator coactivator, but remarkably high levels of these two coactivator proteins were associated with a small set of exceptionally large enhancers. These super-enhancers are associated with genes that feature prominently in MM biology, including the MYC oncogene. Treatment of MM tumor cells with the BET-bromodomain inhibitor JQ1 led to preferential loss of BRD4 at super-enhancers and consequent transcription elongation defects that preferentially impact genes with super-enhancers, including the c-MYC oncogene. Super-enhancers were found at key oncogenic drivers in many other tumor cells. Thus, super-enhancers can regulate oncogenic drivers in tumor cells, which in some cells can be preferentially disrupted by BRD4 inhibition, which in turn contributes to the selective transcriptional effects observed at these oncogenes. These observations have implications for the discovery of novel cancer therapeutics directed at components of super-enhancers in diverse tumor types. Gene expression profiling in multiple myeloma cells after BET-Bromodomain inhibition with JQ1

2013-03-07 | E-GEOD-44929 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data