GSE38234
Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of binding sites in a cell type-specific manner
To obtain an integrated view of gene regulation in response to environmental and endogenous estrogens on a genome-wide scale, we performed ChIP-seq, to identify estrogen receptor 1 (ER) binding sites, and RNA-seq in endometrial cancer cells exposed to bisphenol A (BPA; found in plastics), genistein (GEN; found in soybean), or 17ß-estradiol (E2; an endogenous estrogen).  GEN and BPA treatment induces thousands of ER binding sites and >50 gene expression changes, representing a subset of E2-induced gene regulation changes.  Genes affected by E2 were highly enriched for ribosome-associated proteins; however, GEN and BPA failed to regulate most ribosome-associated proteins and instead enriched for transporters of carboxylic acids.  Treatment-dependent changes in gene expression were associated with treatment-dependent ER binding sites, with the exception that many genes up-regulated by E2 harbored a BPA-induced ER binding site, but failed to show any expression change after BPA treatment.   GEN and BPA exhibited a similar relationship to E2 in the breast cancer line T-47D, where cell type specificity played a much larger role than treatment specificity.  Overall, both environmental estrogens clearly regulate gene expression through ER on a genome-wide scale, although with lower potency resulting in less ER binding sites and less gene expression changes compared to the endogenous estrogen, E2. Overall design: RNA-seq of human cancer cell lines treated with estradiol, bisphenol A, genistein or DMSO (control)