GEO DataSets

(Submitter supplied) Super-enhancers (SEs), which are composed of large clusters of enhancers densely loaded with the Mediator complex, transcription factors and chromatin regulators, drive high expression of genes implicated in cell identity and disease, such as lineage-controlling transcription factors and oncogenes. BRD4 and CDK7 are positive regulators of SE-mediated transcription. By contrast, negative regulators of SE-associated genes have not been well described. more...

Organism:

Homo sapiens

Type:

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

5 related Platforms

89 Samples

Download data: CEL

(Submitter supplied) We characterized the marine natural product cortistatin A (CA) as an inhibitor of CDK8 to determine whether pharmacologic inhibition of CDK8 regulates super-enhancer function and inhibits AML proliferation. In this series, we use ChIP-seq of H3K27ac, H3K4me1, MED1, CDK8, BRD4, and RNA polymerase II (PolII) to examine enhancer occupancy and transcriptional response to CA in human cells lines.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL18573 GPL16791

53 Samples

Download data: BED, XLSX

(Submitter supplied) We characterized the marine natural product cortistatin A (CA) as an inhibitor of CDK8 to determine whether pharmacologic inhibition of CDK8 regulates super-enhancer function and inhibits AML proliferation. In this series, we examine the transcriptional effect on SET2 cells of 4hrs exposure to CA to identify immediate effects.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL17301

6 Samples

Download data: TXT

(Submitter supplied) We characterized the marine natural product cortistatin A (CA) as an inhibitor of CDK8 to determine whether pharmacologic inhibition of CDK8 regulates super-enhancer function and inhibits AML proliferation. In this series, we examine the transcriptional effect on insensitive HCT116 cells of 3hrs exposure to CA.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

6 Samples

Download data: TXT

(Submitter supplied) We characterized the marine natural product cortistatin A (CA) as an inhibitor of CDK8 to determine whether pharmacologic inhibition of CDK8 regulates super-enhancer function and inhibits AML proliferation. In this series, we examine the transcriptional effect on MV4;11 cells of 3hrs exposure to CA to identify immediate effects.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

6 Samples

Download data: CEL

(Submitter supplied) We characterized the marine natural product cortistatin A (CA) as an inhibitor of CDK8 to determine whether pharmacologic inhibition of CDK8 regulates super-enhancer function and inhibits AML proliferation. In this series, we examine the transcriptional effect on MOLM-14 cells of 3hrs exposure to CA to identify immediate effects.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

6 Samples

Download data: CEL

(Submitter supplied) We characterized the marine natural product cortistatin A (CA) as an inhibitor of CDK8 to determine whether pharmacologic inhibition of CDK8 regulates super-enhancer function and inhibits AML proliferation. In this series, we examine the transcriptional effect on MOLM-14 cells of 24hrs exposure to CA.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

6 Samples

Download data: CEL

(Submitter supplied) We characterized the marine natural product cortistatin A (CA) as an inhibitor of CDK8 to determine whether pharmacologic inhibition of CDK8 regulates super-enhancer function and inhibits AML proliferation. In this series, we examine the transcriptional effect on K562 cells of 3hrs exposure to CA to identify immediate effects.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

6 Samples

Download data: CEL

(Submitter supplied) NR4A nuclear receptors are tumor suppressors of acute myeloid leukemia (AML) that are silenced in AML at the level of transcription elongation. Using RNA-Seq, we show that NR4As inhibit leukemic cell growth largely through suppression of MYC pathway genes. MYC is highly expressed in AML and contributes to AML progression and therapeutic resistance. MYC expression in AML is driven by a super enhancer cluster 1.8Mbp downstream of the MYC locus, which is highly sensitive to therapeutic intervention, including treatment with BET inhibitors. more...

Organism:

Homo sapiens

Type:

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

Platform:

GPL18573

15 Samples

Download data: BEDGRAPH, XLSX

(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

Platforms:

GPL23227 GPL18573

38 Samples

Download data: BW

(Submitter supplied) Depletion of CDK8 and its paralogue CDK19, resulted in a global down regulation of mRNA expression, and hence we went to investigate the binding of RNA pol II by ChIP seq at the promoter and at the gene body in the DKO cells. To determine the consequence of loss of CDK8/19 in re-defining enhancers and to underpin the molecular mechanism that providing the preferential BET sensitivity for DKO, we performed ChIP sequencing for MED12, a reminiscent mediator kinase component, BRD4 and H3K27Ac. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL23227

26 Samples

Download data: CSV

(Submitter supplied) Depletion of CDK8 and its paralogue CDK19, resulted in a global down regulation of mRNA expression, and hence we went to investigate the binding of RNA pol II by ChIP seq at the promoter and at the gene body in the DKO cells. To determine the consequence of loss of CDK8/19 in re-defining enhancers and to underpin the molecular mechanism that providing the preferential BET sensitivity for DKO, we performed ChIP sequencing for MED12, a reminiscent mediator kinase component, BRD4 and H3K27Ac. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL18573

12 Samples

Download data: BW

(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) 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:

GPL16791 GPL15207

36 Samples

Download data: CEL, TAR

(Submitter supplied) Despite the development of diagnostic and advanced treatment strategies, the prognosis of patients with osteosarcoma remains poor. A limited understanding of the pathogenesis of osteosarcomas has impeded any improvement in patient outcomes over the past 4 decades. It is thus urgent to identify novel effective targets and treatment regimens for osteosarcoma patients. In this study we delineated the super-enhancer landscape in osteosarcoma cells on the basis of H3K27ac signal intensity by ChIP-Seq and found that super-enhancer-associated genes contribute to the malignant potential of osteosarcoma. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: TAR

(Submitter supplied) CDK7 is a component of the general transcription factor IIH, which regulates RNAPII initiation and elongation.THZ2, a new molecular inhibitor, can completely inhibit the phosphorylation of the established intracellular CDK7 substrate RNAPII CTD at Ser-2, -5 and -7 through irreversible covalent binding to CDK7. Gene expression profiling was then performed to investigate the THZ2-induced transcription effect, and search the subset of sensitive genes in these 2 osteosarcoma cell lines.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL15207

24 Samples

Download data: CEL

(Submitter supplied) Here we describe the development of CKIα inhibitors, which co-target the transcriptional kinases CDK7 and CDK9, thereby augmenting CKIα-induced p53 activation and its anti-leukemic activity. Oncogene-driving super-enhancers (SEs) are highly sensitive to CDK7/9 inhibition. We identified multiple newly-gained SEs in primary mouse AML cells and demonstrate that the inhibitors abolish many SEs and preferentially suppress the transcription elongation of SE-driven oncogenes. more...

Organism:

Mus musculus

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL17021

17 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 array

Platforms:

GPL20301 GPL6244

32 Samples

Download data: BW, CEL

(Submitter supplied) Microarray gene expression profiling was performed in an adult T-cell leukemia/lymphoma cell line (TL-Om1) to analyze genes regulated by the THZ1 CDK7 inhibitor.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL6244

6 Samples

Download data: CEL

(Submitter supplied) ChIP-seq analysis was performed in an adult T-cell leukemia/lymphoma cell line (TL-Om1) to analyze DNA bindings of RNA polymerase II (Pol II) after treatment with the THZ1 CDK7 inhibitor.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL20301

4 Samples

Download data: BW