Identification of Estrogen Receptor Beta Binding Sites in the Human Genomes

Abstract : ER knock-out mice developed prostatic hyperplasia at late age, suggesting an important role of ER in the development of the prostate as well as prostate cancer. Here we describe a study that thoroughly investigates the genomic function of ER . A FLAG-tagged ER was stably expressed in MCF7 C4-12 cells, which allowed ER transcriptional activity to be studied in an ER -independent background. In this cell model, we identified 3166 ER genomic binding sites. Although different from ER genomic binding sites, these ER genomic binding sites had similar global distribution pattern and enriched transcription factor binding motifs to those associated with ER genomic landscape. In conjunction with nascent RNA profiling at the time of ER binding events, ER target genes were found to be enriched in apoptotic and developmental processes. This was in agreement with our result showing that ER suppressed cell growth in response to E2 treatment. Interestingly, 30% of ER binding sites carried EBF1 (Early B-cell Factor 1) binding motif. The interaction between EBF1 and ER correlated with downregulated ER protein stability and downstream activity. Similar phenomenon was observed between EBF1 and ER . These results, at least to our knowlecge, were the first to indicate crosstalk between EBF1 and the estrogen receptors on a large scale.