MCF-7 as a model for functional analysis of breast cancer risk variants

Here we report how the ER+ cell line MCF-7 can be used to inform risk mechanisms for BCa. We identified active regulatory elements (enhancers, promoters, and chromatin organizing elements) by histone H3K27 acetylation and CTCF occupancy and determined the enrichment of risk variants at these sites. We measured gene expression via RNA-seq. After intersection with GWAS risk variants we found 39 enhancers and 15 CTCF occupancy sites that, between them, overlapped 96 BCa credible risk variants at 42 loci. These risk enhancers likely regulate the expression of dozens of genes, which are enriched for GO categories including estrogen and prolactin signaling. Overall design: Two WT MCF-7 samples were used for CTCF ChIP-seq and two for H3k27Ac ChIP-Seq. 8 samples in 2 separate batches, were used for RNA-Seq. These data were compared with publically available data for MCF-7 and HMEC.