BRCA1 Mutations Attenuate Super-Enhancer Function and Chromatin Looping in Haploinsufficient Human Breast Epithelial Cells

BRCA1 functions in multiple biological processes, including double-strand break repair, replication stress suppression, transcriptional regulation, and chromatin reorganization. While non-malignant cells carrying cancer-predisposing BRCA1 mutations exhibit increased genomic instability, it remains unclear whether BRCA1 haploinsufficiency affects transcription and chromatin dynamics. Here we show that primary mammary epithelial cells from women with BRCA1 mutations (BRCA1mut/+) display significant loss of H3K27ac-associated super-enhancers. Overall design: Primary human mammary epithelial cells (HMECs) were isolated from fresh cancer-free breast tissues of BRCA1 mutation carriers (BRCA1mut/+, n = 3) and non-carriers (BRCA1+/+, n = 3), who underwent prophylactic mastectomy and reduction mammoplasty, respectively. H3K27ac chromatin immunoprecipitation with deep-sequencing (ChIP-seq) was performed.