GEO DataSets

(Submitter supplied) 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). more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

13 Samples

Download data: WIG

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL16043 GPL11154

31 Samples

Download data: CEL, WIG

(Submitter supplied) 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). more...

Organism:

Homo sapiens

Type:

Expression profiling by array; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16043

18 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by array; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL11154 GPL6244

28 Samples

Download data: BED, CEL, XLS

(Submitter supplied) We here use B-cell tumors as a model to address the mechanism of action of JQ1, a widely used BET inhibitor.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

22 Samples

Download data: BED, XLS

(Submitter supplied) We here use B-cell tumors as a model to address the mechanism of action of JQ1, a widely used BET inhibitor.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

6 Samples

Download data: CEL, XLS

(Submitter supplied) Following the discovery of BRD4 as a non-oncogene addiction target in acute myeloid leukemia (AML), BET inhibitors are being explored as promising therapeutic avenue in numerous cancers. While clinical trials have reported single-agent activity in advanced hematologic malignancies, mechanisms determining the response to BET inhibition remain poorly understood. To identify factors involved in primary and acquired BET resistance in leukemia, we performed a chromatin-focused shRNAmir screen in a sensitive MLL/AF9; NrasG12D‑driven AML model, and investigated dynamic transcriptional profiles in sensitive and resistant murine and human leukemias. more...

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

6 related Platforms

103 Samples

Download data: BED, BW, GTF, TSV

(Submitter supplied) Bromodomain and extra terminal domain (BET) inhibition reduces occupancy of BET-family proteins at promoter and enhancer sites finally leading to genome wide changes in gene transcription. We used ChIPSeq profiling to investigate genome wide changes in promoter and enhancer occupancy induced by BET inhibitors BAY 1238097 and OTX-015, respectively.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

18 Samples

Download data: BW

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platforms:

GPL11154 GPL18573

65 Samples

Download data: WIG

(Submitter supplied) Triple negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. Here we report the preferential and high sensitivity of TNBCs to BET bromodomain inhibitors such as JQ1 manifested by cell cycle arrest in early G1, apoptosis, and induction of markers of luminal epithelial differentiation in vitro and in vivo. The sensitivity of TNBC and other tumor types to BET inhibition establishes a rationale for clinical investigation, and a motivation to understand mechanisms of resistance. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL18573 GPL11154

28 Samples

Download data: TXT

(Submitter supplied) Triple negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. Here we report the preferential and high sensitivity of TNBCs to BET bromodomain inhibitors such as JQ1 manifested by cell cycle arrest in early G1, apoptosis, and induction of markers of luminal epithelial differentiation in vitro and in vivo. The sensitivity of TNBC and other tumor types to BET inhibition establishes a rationale for clinical investigation, and a motivation to understand mechanisms of resistance. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL11154 GPL18573

35 Samples

Download data: WIG

(Submitter supplied) Triple negative breast cancer (TNBC) is a heterogeneous and clinically aggressive disease for which there is no targeted therapy. Here we report the preferential and high sensitivity of TNBCs to BET bromodomain inhibitors such as JQ1 manifested by cell cycle arrest in early G1, apoptosis, and induction of markers of luminal epithelial differentiation in vitro and in vivo. The sensitivity of TNBC and other tumor types to BET inhibition establishes a rationale for clinical investigation, and a motivation to understand mechanisms of resistance. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

2 Samples

Download data: WIG

(Submitter supplied) Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by early metastasis into lung and bone. Genetically, ES are defined by balanced chromosomal EWS/ETS translocations, which give rise to chimeric proteins (EWS-ETS) that generate an oncogenic transcriptional program associated with altered epigenetic marks throughout the genome. By use of an inhibitor (JQ1) blocking BET bromodomain binding proteins (BRDs) we strikingly observed a strong down-regulation of the predominant EWS-ETS protein EWS/FLI1 in a dose dependent manner. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

4 Samples

Download data: CEL

(Submitter supplied) Diffuse Large B-Cell Lymphoma (DLBCL) is a biologically heterogeneous and clinically aggressive disease. Here, we explore the role of BET bromodomain proteins in DLBCL, using integrative chemical genetics and functional epigenomics. We observe highly asymmetric loading of BRD4 at enhancers, with approximately 33% of all BRD4 localizing to enhancers at 1.6% of occupied genes. These super-enhancers prove particularly sensitive to bromodomain inhibition, explaining the selective effect of BET inhibitors on oncogenic and lineage-specific transcriptional circuits. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

34 Samples

Download data: WIG

(Submitter supplied) To understand the molecular curcuits perturbed by BET bromodoman inhibtion we obtained gene expression profiling of five DLBCL cell lines, SU-DHL6, OCI-Ly1, OCI-Ly4, Toledo and HBL-1, which were treated with either 500nM JQ1 or DMSO for 0,2,6,12,24 and 48hr.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL16522

180 Samples

Download data: CEL

(Submitter supplied) Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric brain tumor with limited therapeutic options. The majority of cases of DIPG exhibit a mutation in histone 3 (H3K27M) that results in oncogenic transcriptional aberrancies. We show here that DIPG is vulnerable to transcriptional disruption using either bromodomain inhibition or CDK7 blockade. We observe that targeting oncogenic transcription through either of these methods synergizes with HDAC inhibition and that DIPG cells resistant to HDAC inhibitor therapy retain sensitivity to CDK7 blockade. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platforms:

GPL20301 GPL18573

26 Samples

Download data: BW, TXT

(Submitter supplied) Genome occupancy profiling by high throughput sequencing

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

4 Samples

Download data: TXT

(Submitter supplied) Genome occupancy profiling by high throughput sequencing

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

8 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

21 Samples

Download data: BIGWIG, TXT

(Submitter supplied) Genome occupancy profiling by high throughput sequencing

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

6 Samples

Download data: TXT