|
| Status |
Public on Oct 13, 2021 |
| Title |
The role of PARP-1 in estrogen-dependent transcription [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Poly (ADP-ribose) polymerase-1 (PARP-1), a multifunctional chromatin-modulating protein, has gained considerable attention as a target for therapeutic inhibitors in breast cancers. Accumulating evidence suggests a pathological role for PARP-1 in breast cancer through its effects on the transcription of tumor-related genes. Here we report the role of PARP-1 in estrogen-dependent transcription in estrogen receptor alpha (ERĪ±)-positive breast cancers. Global nuclear run-on and sequencing (GRO-seq) and RNA-seq analyses suggest that PARP-1 controls the expression of estrogen-regulated genes in ER-positive (ER+) MCF-7 breast cancer cells. Further, ChIP-seq analyses revealed that PARP-1 directly regulates the ligand-dependent binding of ERa and FoxA1 to a subset of its genomic binding sites. Finally, we uncovered that the expression levels of the PARP-1 and estrogen coregulated gene set are enriched in luminal molecular-subtype of breast tumors and high PARP-1 expression in ER+ cases correlates with poor survival. Additionally, treatment with PARP-1 selective inhibitors showed attenuated estrogen-dependent growth of ER+ breast cancer cells. Taken together, the current study suggests that PARP-1 regulates critical molecular pathways that underlie proliferation of ER+ breast cancer cells.
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| Overall design |
Using RNA-seq upon 17b-estradiol (E2) treatment in MCF-7 cells.
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| |
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| Contributor(s) |
Gadad S, Camacho CV, Malladi V, Nagari A, Lee KW |
| Citation(s) |
34158394 |
| |
| Submission date |
May 06, 2021 |
| Last update date |
Oct 13, 2021 |
| Contact name |
W. Lee Kraus |
| E-mail(s) |
[email protected]
|
| Organization name |
UT Southwestern Medical Center
|
| Street address |
5323 Harry Hines Blvd.
|
| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390-8511 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (8)
|
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| This SubSeries is part of SuperSeries: |
| GSE173981 |
The role of PARP-1 in estrogen-dependent transcription |
|
| Relations |
| BioProject |
PRJNA727796 |
| SRA |
SRP318737 |
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