Deepanshu Soota, Bharath Saravanan, Rajat Mann, Tripti Kharbanda, Dimple Notani
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引用次数: 0
摘要
转录因子(TF)通过其 DNA 结合域以不同强度与 DNA 结合,从而调节基因表达。此外,一些转录因子还与 RNA 相互作用,从而调节转录因子与染色质的结合。然而,RNA 介导的 TF 结合是否会导致不同的转录结果仍是未知数。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,它以配体依赖的方式与RNA相互作用。RNA 结合缺陷会导致全基因组范围的 ERα 招募丧失,尤其是在较弱的 ERα 位点。此外,在缺乏 RNA 结合能力的情况下,ERα 在细胞核中的流动性也会增加。意想不到的是,ERα移动性增加的同时,ERα调控基因的聚合酶加载和转录能力也很强,而ERα调控基因中含有低强度的基序。然而,ERα在染色质上的高度稳定结合会对配体依赖性转录产生负面影响。总之,我们的研究结果表明,RNA相互作用在空间上将ERα限制在低亲和力位点上,以微调基因转录。
RNA fine-tunes estrogen receptor-alpha binding on low-affinity DNA motifs for transcriptional regulation.
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.
期刊介绍:
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