Figure 1: ERG opens cryptic AR regulated enhancer in human SOX9 gene. In the absence of ERG, AR binds weakly to a site upstream of the SOX9 gene (S1 site) and weakly suppresses SOX9 expression. In TMPRSS2:ERG fusion positive tumors, ERG binds to a site downstream of the SOX9 gene (S2 site). It then functions in conjunction with FOXA1 as a pioneer transcription factor to open the site and reveal a cryptic AR-binding site, converting the site into an AR-regulated enhancer. The S1 site is highly conserved across species including mouse, but the S2 site is not conserved. AR: androgen receptor.