GSE173976
The role of PARP-1 in estrogen-dependent transcription [RNA-seq]
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 (ERa)-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. Overall design: Using RNA-seq upon 17b-estradiol (E2) treatment in MCF-7 cells.