GEO DataSets

(Submitter supplied) We identified BRD4 as an epigenetic regulator of the prostate lineage specific gene HOXB13 during progression of the disease from an androgen dependent to an androgen independent state.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18460

2 Samples

Download data: TXT

(Submitter supplied) We identified BRD4 as an epigenetic regulator of the prostate lineage specific gene HOXB13 during progression of the disease from an androgen dependent to an androgen independent state.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18460

9 Samples

Download data: TXT

(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:

GPL15433 GPL4133

83 Samples

Download data: BW, TXT

(Submitter supplied) Men who develop metastatic castration-resistant prostate cancer (CRPC) invariably succumb to the disease. The development and progression to CRPC following androgen ablation therapy is predominantly driven by unregulated androgen receptor (AR) signaling1-3. Despite the success of recently approved therapies targeting AR signaling such as abiraterone4-6 and second generation anti-androgens MDV3100 (enzalutamide)7,8, durable responses are limited, presumably due to acquired resistance. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL4133

48 Samples

Download data: TXT

(Submitter supplied) Men who develop metastatic castration-resistant prostate cancer (CRPC) invariably succumb to the disease. The development and progression to CRPC following androgen ablation therapy is predominantly driven by unregulated androgen receptor (AR) signaling1-3. Despite the success of recently approved therapies targeting AR signaling such as abiraterone4-6 and second generation anti-androgens MDV3100 (enzalutamide)7,8, durable responses are limited, presumably due to acquired resistance. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL15433

35 Samples

Download data: BW

(Submitter supplied) To understand the mechanistic role of HOXB13 lysine acetylation in CRPC development andd progression, differential gene expression analysis was performed following RNA-sequencing of the HOXB13K13A mutant versus the isogenic parental C4-2B to identify bonafide transcriptional targets of acetylated HOXB13. Chromatin remodeling and self-renewal genes were significantly impacted as a result of HOXB13-K13 mutation. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

5 Samples

Download data: TXT

(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:

GPL21290 GPL24676

17 Samples

Download data

(Submitter supplied) While tissue and lineage-specific super-enhancers (SEs) regulate cell fate decision during development, the nature of Castration Resistant Prostate Cancer (CRPC)-specific SEs (CSEs) that drive resistance to AR-targeted therapies is unknown. Herein we report the lysine 13 (K13)-acetylation of Homeodomain transcription factor HOXB13 as a critical feature underlying CSE exclusivity. The histone acetyltransferase (HAT) CBP/p300 specifically acetylates HOXB13 (acK13-HOXB13) in prostate cancer cells. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL21290

7 Samples

Download data: BIGWIG, NARROWPEAK

(Submitter supplied) Treatment induced-resistance of CRPC is an imminent undesirable outcome in patients. Tissue and lineage-specific super-enhancers (SEs) determine cell fate and plasticity during development and disease respectively. However, the identity and function of CRPC-specific SEs (CSEs) regulated genes is unknown. Herein we report the lysine 13 acetylation of the prostate-enriched transcription factor HOXB13 (acK13-HOXB13) mediated by the histone acetyl transferase (HAT) CBP/p300 as a critical mechanism of CSE establishment. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL21290

5 Samples

Download data: BIGWIG, NARROWPEAK

(Submitter supplied) While tissue and lineage-specific super-enhancers (SEs) regulate cell fate decision during development, the nature of Castration Resistant Prostate Cancer (CRPC)-specific SEs (CSEs) is unknown. Herein we report the lysine 13 (K13) acetylation of HOXB13 mediated by the histone acetyltransferase CBP/p300 regulates prostate tumor autonomy. The acK13-HOXB13 shadows H3K27ac at lineage specific SEs and surpasses it at CSEs. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

1 Sample

Download data: H5

(Submitter supplied) The constitutively active androgen receptor (AR) splice variant 7 (AR-V7) plays an important role in the progression of castration-resistant prostate cancer (CRPC). Although biomarker studies established the role of AR-V7 in resistance to AR-targeting therapies, how AR-V7 mediates genomic functions in CRPC remains largely unknown. Using a ChIP-exo approach, we show AR-V7 binds to distinct genomic regions and recognizes a full-length androgen-responsive element in CRPC cells and patient tissues. more...

Organism:

Homo sapiens

Type:

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

Platforms:

GPL11154 GPL20301

40 Samples

Download data: BEDGRAPH, BW, TXT

(Submitter supplied) Competitive inhibitors of acetyl-lysine binding to the bromodomains of the BET (bromodomain and extra terminal) family are being developed for the treatment of solid and heme malignancies. BET family member BRD4 function at enhancers/super-enhancers has been shown to sustain signal-dependent or pathogenic gene expression programs. Here we tested the hypothesis that the transcription factor drivers of castration-resistant prostate cancer (CRPC) clinical progression, including the Androgen Receptor (AR), are critically dependent on BRD4 and thus represent a sensitive solid tumor indication for the BET inhibitor ABBV-075. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

8 Samples

Download data: CEL

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

Organism:

Homo sapiens

Type:

Expression profiling by array; Genome variation profiling by genome tiling array

Platforms:

GPL14550 GPL10123 GPL10152

56 Samples

Download data: TXT

(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) BET bromodomain inhibitors are known to block prostate cancer cell survival through suppression of c-Myc and androgen receptor (AR) function. However, little is known about other transcriptional modulators whose function is blocked by these drugs and the anti-tumor activity of BET bromodomain inhibition in AR-independent castration-resistant prostate cancers (CRPC), whose frequency may be increasing. more...

Organism:

Homo sapiens

Type:

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

Platform:

GPL11154

34 Samples

Download data: BED, TXT

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

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21290

20 Samples

Download data

(Submitter supplied) Here we report the discovery of ABBV-744, a first in class, highly potent and selective inhibitor of BET family BD2 domains with drug like properties. RNA-seq analysis revealed that ABBV-744 elicited potent inhibition of AR-dependent transcription without causing broad transcription alterations associated with exposure to pan BET inhibitors.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21290

10 Samples

Download data: TXT