GSE131436
Genome-wide analysis of histone 3 lysine K27 acetylation in stem-like breast cancer cells in response to HDAC1/3/7 inhibition.
We sought to investigate the effects of HDAC1 and HDAC7 inhibition on genome-wide histone 3 lysine 27 acetylation (H3K27ac) in BPLER cells, a stem-like breast cancer (BrCa) cell model (please search for keyword "BPLER" in GEO to access over 30 associated datasets). Treatment of BPLER cells with MS-275 (Entinostat), a HDAC1 and HDAC3 specific inhibitor, specifically downregulates HDAC7 mRNA and protein. We carried out ChIP-seq analysis in BPLER cells treated with MS-275 and found that HDAC1/3/7 inhibition is associated with a decrease in H3K27ac at transcription start sites (TSS) and super-enhancers (SE) in stem-like BrCa cells. Importantly, these changes in chromatin landscape reduced H3K27ac at many SE-associated oncogenes, including c-MYC, CD44, CDKN1B, SLUG, VDR, SMAD3, VEGFA and XBP1. Our findings suggest that inactivation of HDAC1/3-HDAC7 axis may inhibit SE-associated oncogene expression in cancer stem cells, which can be a promising pathway to target for developing novel BrCa therapies. Overall design: H3K27ac profiling in stem-like BrCa cells treated with MS-275 (Entinostat).