Transcription factors (TFs) regulate gene expression by binding with varying strengths to DNA via their DNA-binding domain. Additionally, some TFs also interact with RNA, which modulates transcription factor binding to chromatin. However, whether RNA-mediated TF binding results in differential transcriptional outcomes remains unknown. In this study, we demonstrate that estrogen receptor α (ERα), a ligand-activated TF, interacts with RNA in a ligand-dependent manner. Defects in RNA binding lead to genome-wide loss of ERα recruitment, particularly at weaker ERα-motifs. Furthermore, ERα mobility in the nucleus increases in the absence of its RNA-binding capacity. Unexpectedly, this increased mobility coincides with robust polymerase loading and transcription of ERα-regulated genes that harbor low-strength motifs. However, highly stable binding of ERα on chromatin negatively impacts ligand-dependent transcription. Collectively, our results suggest that RNA interactions spatially confine ERα on low-affinity sites to fine-tune gene transcription.

中文翻译：

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RNA 微调雌激素受体-α 与低亲和力 DNA 基序的结合，以进行转录调控。


转录因子 （TFs） 通过其 DNA 结合结构域以不同强度与 DNA 结合来调节基因表达。此外，一些 TF 还与 RNA 相互作用，RNA 调节转录因子与染色质的结合。然而，RNA 介导的 TF 结合是否会导致差异转录结局仍是未知数。在这项研究中，我们证明了雌激素受体 α （ERα） 是一种配体激活的 TF，以配体依赖性方式与 RNA 相互作用。RNA 结合缺陷导致 ERα 募集在全基因组范围内丢失，尤其是在较弱的 ERα 基序上。此外，在没有 RNA 结合能力的情况下，细胞核中的 ERα 迁移率增加。出乎意料的是，这种增加的迁移率与强大的聚合酶负载和含有低强度基序的 ERα 调节基因的转录相吻合。然而，ERα 与染色质的高度稳定结合会对配体依赖性转录产生负面影响。总的来说，我们的结果表明，RNA 相互作用在空间上将 ERα 限制在低亲和力位点以微调基因转录。