ATAC-seq analyses of AR-V7.. ATAC-seq analyses of AR-V7.

Although AR-V7 has been intensively studied, it remains unclear whether AR-V7 and other AR splicing variants can specifically activate a distinctive transcriptional program from the full-length AR (AR-FL), and whether AR-V7 may play a role in accelerating the metastatic progression of castration-resistant PCa (CRPC). In this study, we hypothesize that AR-V7 can drive a distinct transcription program from AR-FL in CRPC condition. To test this, we performed ATAC-seq using LNCaP model with inducible overexpression of AR-V7 to examine the function of AR-V7. We demonstrated that AR-V7 has “pioneer factor-like” activities to access the androgen-responsive elements (AREs) located at compact chromatin regions. More importantly, we found that SOX9, a critical metastasis driver gene, was a direct target and downstream effector of AR-V7, and its protein expression was dramatically upregulated at AR-V7-induced bone lesions. Overall design: ATAC-seq analyses in LNCaP table cells with or without overexpression of AR-V7 and stimulated with or without DHT under 5% charcoal-stripped FBS condition. The stable cells were generated by stably infecting LNCaP cells with tetracycline inducible overexpression of wild-type AR-V7 virus. These stable cells were grown in the medium containing 10% tetracycline-free FBS.