Genome-wide activity of unliganded Estrogen Receptor alpha in breast cancer cells [ChIP-Seq]. Homo sapiens

Estrogen Receptor α (ERα) has central role in hormone-dependent breast cancer and its ligand-induced functions have been extensively characterized. However, evidence exists that ERα has functions which are independent of ligands. In the present work, we investigated the binding of ERα to chromatin in absence of ligands, and its function(s) on gene regulation. We demonstrated that in MCF7 breast cancer cells unliganded ERα binds to more than four thousands chromatin sites. Unexpectedly, although almost entirely comprised in the larger group of estrogen-induced binding sites, we found that unliganded-ERα binding is specifically linked to genes with developmental functions, as compared to estrogen-induced binding. Moreover, we found that siRNA-mediated downregulation of ERα in absence of estrogen is accompanied by changes in the expression levels of hundreds of coding and noncoding RNAs. Downregulated mRNAs showed enrichment in genes related to epithelial cell growth and development. Stable ERα downregulation using shRNA, which caused cell-growth arrest, was accompanied by increased H3K27me3 at ERα binding sites. Finally, we found that FOXA1 and AP2γ binding to several sites is decreased upon ERα silencing, suggesting that unliganded ERα participates, together with other factors, to the maintenance of the luminal-specific cistrome in breast cancer cells. Overall design: Examination of unliganded estrogen receptor alpha (ERα) DNA interactions in control and ERα siRNA treated MCF7 cells.