Genome-wide mapping of FOXM1 binding reveals co binding with estrogen receptor alpha in breast cancer cells

The study utilizes chromatin immunoprecipitation followed by high-throughput sequencing to map FOXM1 binding in both ERalpha positive and negative breast cancer cell lines. The comparison between binding site distributions in the two cell lines uncovered a previously undescribed relationship between binding of FOXM1 and ERalpha. Further molecular analyses demonstrated that these two factors can bind simultaneously at genomic sites and furthermore that FOXM1 regulates the transcriptional activity of ERalpha via interaction with the coactivator CARM1. Inhibition of FOXM1 activity using the natural product thiostrepton revealed down-regulation of a set of FOXM1 regulated genes that are correlated with patient outcome in clinical breast cancer samples.These findings reveal a novel role for FOXM1 in ERalpha transcriptional activity in breast cancer and uncover a FOXM1-regulated gene signature associated with ER positive breast cancer patient prognosis.