Figure 6. A Model for TOP1-mediated Activation of the AR-Enhancer.
Following androgen stimulation, AR and DNA topoisomerase I recruit to the enhancer region, premarked by the NKX3.1 pioneer transcription factor. NKX3.1 to TOP1 stimulates enzymatic activity of the topoisomerase, resulting in nicking of DNA on a single strand, followed by recruitment of ATR, XRCC1, and the MRN complex components (MRE11/RAD50). After dismissal of TOP1, ATR and the MRN, additional components of DNA repair machinery recruit to the activated enhancer. The “thin blue line” indicates the presence of low levels of residual eRNA, not totally eliminated by hormone starvation, whereas the “thick blue line” represents induced bidirectional eRNA produced by the transcription unit.