In mammals, argonaute (AGO) proteins have been characterized for their roles in small RNA–mediated posttranscriptional and also in transcriptional gene silencing. Here, we report a different role for AGO1 in estradiol-triggered transcriptional activation in human cells. We show that in MCF-7 mammary gland cells, AGO1 associates with transcriptional enhancers of estrogen receptor α (ERα) and that this association is up-regulated by treating the cells with estrogen (E2), displaying a positive correlation with the activation of these enhancers. Moreover, we show that AGO1 interacts with ERα and that this interaction is also increased by E2 treatment, but occurs in the absence of RNA. We show that AGO1 acts positively as a coactivator in estradiol-triggered transcription regulation by promoting ERα binding to its enhancers. Consistently, AGO1 depletion decreases long-range contacts between ERα enhancers and their target promoters. Our results point to a role of AGO1 in transcriptional regulation in human cells that is independent from small RNA binding.

中文翻译：

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人类 Argonaute-1 作为雌激素依赖性转录共激活剂的核作用

在哺乳动物中，argonaute (AGO) 蛋白因其在小 RNA 介导的转录后和转录基因沉默中的作用而被表征。在这里，我们报告了 AGO1 在雌二醇触发的人类细胞转录激活中的不同作用。我们发现，在 MCF-7 乳腺细胞中，AGO1 与雌激素受体 α (ERα) 的转录增强子相关，并且这种关联通过用雌激素 (E2) 处理细胞而上调，与这些细胞的激活呈正相关。增强剂。此外，我们发现 AGO1 与 ERα 相互作用，并且这种相互作用也通过 E2 处理而增强，但发生在没有 RNA 的情况下。我们发现 AGO1 通过促进 ERα 与其增强子结合，在雌二醇触发的转录调控中发挥积极的共激活子作用。一致地，AGO1 耗尽会减少 ERα 增强子与其目标启动子之间的长程接触。我们的结果表明 AGO1 在人类细胞转录调控中的作用独立于小 RNA 结合。