|
| Status |
Public on May 02, 2015 |
| Title |
H4K12ac is regulated by estrogen receptor-alpha and is associated with BRD4 function and inducible transcription |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Hormone-dependent gene expression requires dynamic and coordinated epigenetic changes. Estrogen receptor-positive (ER+) breast cancer is particularly dependent upon extensive chromatin remodeling and changes in histone modifications for the induction of hormone-responsive gene expression. Our previous studies established an important role of bromodomain-containing protein-4 (BRD4) in promoting estrogen-regulated transcription and proliferation of ER+ breast cancer cells. Here, we investigated the association between genome-wide occupancy of histone H4 acetylation at lysine 12 (H4K12ac) and BRD4 in the context of estrogen-induced transcription. Similar to BRD4, we observed that H4K12ac occupancy increases near the transcription start sites (TSS) of estrogen-induced genes as well as at distal ERα binding sites in an estrogen-dependent manner. Interestingly, H4K12ac occupancy highly correlates with BRD4 binding and enhancer RNA production on ERα-positive enhancers. Consistent with an importance in estrogen-induced gene transcription, H4K12ac occupancy globally increased in ER-positive cells relative to ER-negative cells and these levels were further increased by estrogen treatment in an ERα-dependent manner. Together, these findings reveal a strong correlation between H4K12ac and BRD4 occupancy with estrogen-dependent gene transcription and further suggest that modulators of H4K12ac and BRD4 may serve as new therapeutic targets for hormone-dependent cancers.
|
| |
|
| Overall design |
ChIP-seq profiles of H4K12ac in MCF7 cells treated with +/- estrogen treatment and MCF10A cells.
|
| |
|
| Contributor(s) |
Nagarajan S, Johnsen SA |
| Citation(s) |
25788266 |
| Submission date |
Feb 12, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Steven A Johnsen |
| E-mail(s) |
sjohnsen@alumni.mayo.edu
|
| Organization name |
University Medical Center Göttingen
|
| Department |
Department of General, Visceral and Pediatric Surgery
|
| Street address |
Robert-Koch-Straße 40
|
| City |
Göttingen |
| State/province |
Niedersachsen |
| ZIP/Postal code |
37075 |
| Country |
Germany |
| |
|
| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
|
| Samples (8)
|
|
| Relations |
| BioProject |
PRJNA275306 |
| SRA |
SRP054970 |
Less...
More...