GEO DataSets

(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) 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) 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) Aberrant changes in microRNAs (miRNAs) contribute to lymphomagenesis and represent potential therapeutic targets. OTX015 (MK-8628), a bromodomain and extra-terminal domain (BET) inhibitor (BETi), has demonstrated preclinical and clinical activity in haematological tumours. To better understand the mechanism of action of OTX015 we studied its effects on miRNAs in lymphomas. We performed miRNA profiling of DLBCL cells treated with OTX015 and observed changes in the expression levels of a subset of miRNAs, including miR-92a-1-5p, miR-21-3p, miR-155-5p and miR-96-5p, which are known to play a role in lymphomagenesis and/or resistance to chemotherapy. more...

Organism:

Homo sapiens

Type:

Expression profiling by array; Other

Platforms:

GPL21799 GPL17841 GPL23507

96 Samples

Download data: TXT

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

Organism:

Homo sapiens

Type:

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

Platforms:

GPL11154 GPL18573

80 Samples

Download data: BED, BEDGRAPH, FPKM_TRACKING

(Submitter supplied) Circular chromatin confirmation capture in rhabdomyosarcoma cells was performed with viewpoints at the PAX3-FOXO1 bound super enhancer upstream of MYOD1, and also at the MYOD1 promoter, to find support for looping between these two genetic elements almost 80 thousand base pairs apart.

Organism:

Homo sapiens

Type:

Other

Platform:

GPL18573

2 Samples

Download data: BEDGRAPH

(Submitter supplied) The fusion transcription factor PAX3-FOXO1 drives oncogenesis in a subset of rhabdomyosarcomas, however the mechanisms by which it remodels chromatin are unknown. We find PAX3-FOXO1 reprograms the cis-regulatory landscape by inducing super enhancers (SEs), in collaboration with master transcription factors MYOG, MYOD and MYCN. This myogenic SE circuitry is consistent across cell lines and primary tumors. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL18573 GPL11154

54 Samples

Download data: BED

(Submitter supplied) The fusion transcription factor PAX3-FOXO1 drives oncogenesis in a subset of rhabdomyosarcomas, however the mechanisms by which it remodels chromatin are unknown. We find PAX3-FOXO1 reprograms the cis-regulatory landscape by inducing super enhancers (SEs), in collaboration with master transcription factors MYOG, MYOD and MYCN. This myogenic SE circuitry is consistent across cell lines and primary tumors. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL18573 GPL11154

14 Samples

Download data: BED

(Submitter supplied) The fusion transcription factor PAX3-FOXO1 drives oncogenesis in a subset of rhabdomyosarcomas, however the mechanisms by which it remodels chromatin are unknown. We find PAX3-FOXO1 reprograms the cis-regulatory landscape by inducing super enhancers (SEs), in collaboration with master transcription factors MYOG, MYOD and MYCN. This myogenic SE circuitry is consistent across cell lines and primary tumors. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL11154 GPL18573

10 Samples

Download data: FPKM_TRACKING

(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) 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

37 Samples

Download data: BIGWIG, TXT

(Submitter supplied) The bromodomain and extraterminal (BET) protein Brd4 is a validated drug target in leukemia, yet its regulatory function in this disease is not well understood. Here, we show that Brd4 chromatin occupancy in acute myeloid leukemia closely correlates with the hematopoietic transcription factors (TFs) Pu.1, Fli1, Erg, C/EBPα, C/EBPβ, and Myb at nucleosome-depleted enhancer and promoter regions. We provide evidence that these TFs, in conjunction with the lysine acetyltransferase activity of p300/CBP, facilitate Brd4 recruitment to their occupied sites to promote transcriptional activation. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL13112

29 Samples

Download data: BIGWIG

(Submitter supplied) The bromodomain and extraterminal (BET) protein Brd4 is a validated drug target in leukemia, yet its regulatory function in this disease is not well understood. Here, we show that Brd4 chromatin occupancy in acute myeloid leukemia closely correlates with the hematopoietic transcription factors (TFs) Pu.1, Fli1, Erg, C/EBPα, C/EBPβ, and Myb at nucleosome-depleted enhancer and promoter regions. We provide evidence that these TFs, in conjunction with the lysine acetyltransferase activity of p300/CBP, facilitate Brd4 recruitment to their occupied sites to promote transcriptional activation. more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

8 Samples

Download data: TXT

(Submitter supplied) Technical replicates from BC3 and BCBL1 cell lines were treated with DMSO or 5 micromoles of lenalidomide for 24 hours. NOTE: Detection p-values were neither computed nor used in this experiment. All data was processed directly from IDATs and the proportion of present probes estimated from the negative and positive controls.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

8 Samples

Download data: IDAT, TXT

(Submitter supplied) Bromodomain inhibition comprises a promising therapeutic strategy in cancer, particularly for hematologic malignancies. To date, however, genomic biomarkers to direct clinical translation have been lacking. We conducted a cell-based screen of genetically-defined cancer cell lines using a prototypical inhibitor of BET bromodomains. Integration of genetic features with chemosensitivity data revealed a robust correlation between MYCN amplification and sensitivity to bromodomain inhibition. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL15207

12 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below. Super-enhancers are an emerging sub-class of regulatory regions controlling cell identity and disease genes. However, their biological function and impact on miRNA networks are unclear. Here we report that super-enhancers drive the biogenesis of master miRNAs crucial for cell identity by enhancing both transcription and Drosha/DGCR8-mediated primary miRNA processing. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing; Other; Non-coding RNA profiling by high throughput sequencing

Platforms:

GPL19057 GPL13112

15 Samples

Download data: BW