Regulation of FOXA1 protein stability by Polycomb and BUB3/USP7 deubiquitin complexes in prostate cancer [ChIP-Seq]

FOXA1 transcription factor is essential for the development and maturation of prostate luminal epithelial cells. FOXA1 gene is frequently mutated and its expression is deregulated during prostate cancer progression. We and others have shown that FOXA1 induces androgen-dependent cell growth by transcriptional regulation of target genes related to cell cycle process, DNA replication, cell division, and apoptosis. Despite of its important roles, how FOXA1 expression itself is regulated in prostate cancer cells remains largely unknown. Here we report that EZH2 methylates one of the lysine residues (K295) on FOXA1 protein to reduce its ubiquitination and subsequent degradation. Mechanistically, this EZH2-mediated FOXA1 methylation recruits BUB3/USP7 deubiquitinase complex to remove FOXA1 ubiquitination for increased protein stability. ChIP-seq of prostate cancer cells with FOXA1 de-regulation or inhibition