|
| Status |
Public on Sep 22, 2022 |
| Title |
HOXB13 epigenome in castration-resistant prostate cancer |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
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. Mechanistically, acK13-HOXB13 establishes the CRPC enhanceosome comprising chromatin remodeling bromo-domain proteins SMARCA2/BAZ2B and the HAT p300/CBP which enable histone and non-histone protein acetylation at CSEs. Such CSEs sprout at tyrosine kinase genes encoding ACK1/TNK2, VEGFA, and ANGPT2/ANGPTL3 to increase pathogenic output in primary human tumors. These tyrosine kinase mediated signaling cascades establish robust networks to conduce growth, survival and androgen-bypass. Consistently, the loss of function acK13-HOXB13 mutants show significant reduction of proliferation, spheroid formation, and xenograft tumor growth that correlates with the high sensitivity to the AR-antagonist Enzalutamide. Targeting HOXB13 acetylation mediated CRPC-SE establishment at critical tyrosine kinase genes could therefore have significant clinical implications in preventing PC recurrence.
|
| |
|
| Overall design |
Genome-wide binding site analysis of HOXB13 in chromatin extracts prepared from prostate cancer cell lines.
|
| |
|
| Contributor(s) |
Mahajan K |
| Citation(s) |
35849143 |
| |
| Submission date |
Mar 17, 2021 |
| Last update date |
Sep 22, 2022 |
| Contact name |
Kiran Mahajan |
| E-mail(s) |
[email protected]
|
| Phone |
3142737728
|
| Organization name |
Washington University
|
| Department |
Surgery
|
| Lab |
Kiran Mahajan Lab
|
| Street address |
CB 8242 600 South Euclid Ave
|
| City |
St. Louis |
| State/province |
Missouri |
| ZIP/Postal code |
63110 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
|
| Samples (5)
|
|
| This SubSeries is part of SuperSeries: |
| GSE169134 |
Targeted Escalation of Acetylated HOXB13 Regulated Super-Enhancers Promotes Prostate Tumor Autonomy |
|
| Relations |
| BioProject |
PRJNA715287 |
| SRA |
SRP311157 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE169132_hoxb13-1_minus_igg.fc.signal.bigwig |
1.0 Gb |
(ftp)(http) |
BIGWIG |
| GSE169132_hoxb13-1_minus_igg.filt.narrowPeak.gz |
643.1 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE169132_hoxb13-1_minus_input.fc.signal.bigwig |
1.1 Gb |
(ftp)(http) |
BIGWIG |
| GSE169132_hoxb13-1_minus_input.filt.narrowPeak.gz |
571.0 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE169132_hoxb13-2_minus_igg.fc.signal.bigwig |
973.3 Mb |
(ftp)(http) |
BIGWIG |
| GSE169132_hoxb13-2_minus_igg.filt.narrowPeak.gz |
569.9 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE169132_hoxb13-2_minus_input.fc.signal.bigwig |
1.1 Gb |
(ftp)(http) |
BIGWIG |
| GSE169132_hoxb13-2_minus_input.filt.narrowPeak.gz |
468.8 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE169132_rna_pol_ii_minus_igg.fc.signal.bigwig |
1.0 Gb |
(ftp)(http) |
BIGWIG |
| GSE169132_rna_pol_ii_minus_igg.filt.narrowPeak.gz |
910.8 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE169132_rna_pol_ii_minus_input.fc.signal.bigwig |
1.1 Gb |
(ftp)(http) |
BIGWIG |
| GSE169132_rna_pol_ii_minus_input.filt.narrowPeak.gz |
526.3 Kb |
(ftp)(http) |
NARROWPEAK |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
Less...
More...