雄激素受体（AR）具有转抑制效应的发现，完善了其作为典型转录因子的功能圈子，其固有地具有激活和抑制的双重功能，与共因子竞争和重分布相关。的确，AR的双重功能由可调控致癌基因位点8q24-MYC区域的全基因组调控所示。用RT-qPCR测定及名义RNA分析数据库来评估雄激素敏感细胞系中的MYC转录。计算名义CHIP-seq和RNA-Seq数据库来评估AR-MYC的直接和间接特征。监测典型的MYC和AR通路中基因集来验证它们之间的相互作用。在AR基因位点进行生物信息学和染色体构象捕获（3C）实验，以检查雄激素诱导的远端调控。最后，在AR结合位点和MYC结合位点之间全局跟踪共因子重分布。在本研究中，我们发现MYC对雄激素具有超敏感的负反应，与AR作为固有雄激素效应物的自然功能相媲美。此外，AR和MYC的直接和间接转录程序均得到积极平衡。通过建立雄激素介导和MYC介导的基因子集，我们验证了AR和MYC通路都是双向且广泛交错的。另外，我们确定AR基因位点类似于MYC基因区域，两个基因位点都通过表观遗传学和染色质结构改变被雄激素抑制。值得注意的是，沿前列腺癌（PCa）基因组的转录因子的分布揭示了PCa转录组在AR结合位点和MYC结合位点之间动态平衡。综上所述，我们的发现揭示了广泛、精巧组织的AR-MYC相互作用来补偿必要的PCa转录程序并抵消过度信号。© 2023 Wiley Periodicals LLC.

The discovery of androgen receptor (AR) having transrepression effects completes the circle of its functionalities as a typical transcription factor, which intrinsically bears dual functions of activation and repression linked to co-factor competition and redistribution. Indeed, AR dual functions are exemplified by locus-wide regulation of the oncogenic 8q24-MYC region.RT-qPCR assay and public RNA-profiling datasets were used to assess MYC transcription in androgen-sensitive cell lines. Public ChIP-seq and RNA-Seq datasets were computed to evaluate AR-MYC direct and indirect signatures. Gene sets in typical MYC and AR pathways were monitored to validate their cross-talks. Bio-informatics and chromosome conformation capture (3C) assay were performed in the AR gene locus to examine androgen-elicited distal regulation. Finally, co-factor re-distribution were globally tracked between AR and MYC binding sites.In this report, we found MYC responded negatively to androgen with hypersensitivity, rivaling AR natural functions as an innate androgen effector. Furthermore, both direct and indirect AR and MYC transcriptional programs were actively in equilibration. With established androgen-mediated versus MYC-mediated gene subsets, we validated AR and MYC pathways were both bidirectional and extensively entangled. In addition, we determined that the AR gene locus resembled the MYC gene region and both loci were androgen-repressed via epigenetics and chromatin architectural alterations. Significantly, transcriptional factor profiling along the prostate cancer (PCa) genome exposed that PCa transcriptomes were dynamically equilibrated between AR-binding site and MYC-binding site.Together, our findings stratified AR-MYC interactions that are extensively wired and intricately organized to compensate for essential PCa transcriptional programs and neutralize excessive signaling.© 2023 Wiley Periodicals LLC.