Embryonic stem cells (ESCs) exhibit high levels of ribosomal RNA (rRNA) transcription and ribosome biogenesis. Here, we reveal an unexpected role for an essential DEAD-box helicase, DDX18, in antagonizing the polycomb repressive complex 2 (PRC2) to prevent deposition of the repressive H3K27me3 mark onto rDNA in pluripotent cells. DDX18 binds and sequesters PRC2 in the outer layer of the nucleolus and counteracts PRC2 complex formation in vivo and in vitro. DDX18 knockdown leads to increased occupancy of PRC2 and H3K27me3 at rDNA loci, accompanied by drastically decreased rRNA transcription and reduced ribosomal protein expression and translation. Auxin-induced rapid degradation of DDX18 enhances PRC2 binding at rDNA. The inhibition of PRC2 partially rescues the effects of DDX18 depletion on rRNA transcription and ESC self-renewal. These results demonstrate a critical role for DDX18 in safeguarding the chromatin and transcriptional integrity of rDNA by counteracting the epigenetic silencing machinery to promote pluripotency.

中文翻译：

---

DEAD-Box解旋酶18在多能性调节中抵消PRC2来保护核糖体DNA。

胚胎干细胞（ESC）表现出高水平的核糖体RNA（rRNA）转录和核糖体生物发生。在这里，我们揭示了一种必不可少的DEAD-box解旋酶DDX18在拮抗多梳阻抑复合物2（PRC2）方面的作用，以防止阻抑性H3K27me3标记沉积在多能细胞中的rDNA上。DDX18在核仁的外层结合并隔离PRC2，并在体内和体外抵消PRC2复合物的形成。DDX18敲低导致rDNA基因座上PRC2和H3K27me3的占据增加，同时伴随着rRNA转录的急剧下降以及核糖体蛋白表达和翻译的减少。生长素诱导的DDX18的快速降解增强了rDNA上PRC2的结合。PRC2的抑制部分挽救了DDX18耗竭对rRNA转录和ESC自我更新的影响。