Androgen induces the binding of its receptor (AR) to androgen-responsive elements (AREs), while genome-wide studies showed that most androgen-induced AR binding sites on chromatin were unrelated to AREs. Enhancer RNAs (eRNAs), a class of noncoding RNAs (ncRNAs), are transcribed from superenhancers (SEs) and trigger the formation of large ribonucleoprotein condensates of transcription factors. By in silico search, an SE is found to be located on the locus of KLK3 that encodes prostate specific antigen. On the KLK3 SE, androgen-induced expression of ncRNAs was detected and designated as KLK3eRNAs in LNCaP cells, and androgen-induced association of AR and FOXA1 on the KLK3eRNA coding regions was detected. Such androgen-induced association of an AR mutant lacking DNA binding activity on the KLK3eRNA coding regions was undetectable on an exogenous ARE. Thus, the present findings suggest a molecular basis of androgen-induced association of AR with chromatin on ARE-unrelated sequences.

中文翻译：

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雄激素受体与编码雄激素诱导的非编码RNA的彩色区域的雄激素依赖性和DNA结合非依赖性关联。


雄激素诱导其受体 (AR) 与雄激素反应元件 (ARE) 结合，而全基因组研究表明，染色质上大多数雄激素诱导的 AR 结合位点与 ARE 无关。增强子 RNA (eRNA) 是一类非编码 RNA (ncRNA)，由超级增强子 (SE) 转录，并触发转录因子大核糖核蛋白凝聚物的形成。通过计算机搜索，发现SE位于编码前列腺特异性抗原的KLK3基因座上。在 KLK3 SE 上，检测到雄激素诱导的 ncRNA 表达，并将其命名为 LNCaP 细胞中的 KLK3eRNA，并检测到雄激素诱导的 KLK3eRNA 编码区上 AR 和 FOXA1 的关联。在 KLK3eRNA 编码区上缺乏 DNA 结合活性的 AR 突变体的这种雄激素诱导的关联在外源 ARE 上是检测不到的。因此，目前的研究结果表明雄激素诱导的 AR 与 ARE 不相关序列上的染色质关联的分子基础。