Liver regeneration and metabolism are highly interconnected. Here, we show that hepatocyte-specific ablation of RNA polymerase II (Pol II)-associated Gdown1 leads to down-regulation of highly expressed genes involved in plasma protein synthesis and metabolism, a concomitant cell cycle re-entry associated with induction of cell cycle-related genes (including cyclin D1), and up-regulation of p21 through activation of p53 signaling. In the absence of p53, Gdown1-deficient hepatocytes show a severe dysregulation of cell cycle progression, with incomplete mitoses, and a premalignant-like transformation. Mechanistically, Gdown1 is associated with elongating Pol II on the highly expressed genes and its ablation leads to reduced Pol II recruitment to these genes, suggesting that Pol II redistribution may facilitate hepatocyte re-entry into the cell cycle. These results establish an important physiological function for a Pol II regulatory factor (Gdown1) in the maintenance of normal liver cell transcription through constraints on cell cycle re-entry of quiescent hepatocytes.

中文翻译：

---

Gdown1切除对代谢基因的转录下调会诱导静态细胞重新进入细胞周期。

肝脏的再生和新陈代谢高度相关。在这里，我们显示RNA聚合酶II（Pol II）相关的Gdown1的肝细胞特异性消融导致参与血浆蛋白合成和代谢的高表达基因的下调，伴随细胞周期诱导而伴随的细胞周期再进入相关基因（包括cyclin D1）和p21的上调通过激活p53信号。在缺乏p53的情况下，缺乏Gdown1的肝细胞显示出严重的细胞周期进程失调，有丝分裂不完全和恶变前样转化。从机制上讲，Gdown1与延长高表达基因上的Pol II有关，其消融导致Pol II对这些基因的募集减少，这表明Pol II的重新分布可能促进肝细胞重新进入细胞周期。这些结果通过限制静态肝细胞的细胞周期重新进入，在维持正常肝细胞转录中为Pol II调节因子（Gdown1）建立了重要的生理功能。