Human PIH1 associates with histone H4 to mediate the glucose-dependent enhancement of pre-rRNA synthesis.
Human PIH1 associates with histone H4 to mediate the glucose-dependent enhancement of pre-rRNA synthesis.
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DOI：
10.1093/jmcb/mjs003
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发表时间：
2012-08
影响因子：
5.5
通讯作者：
Niu Zhai;Zhong-liang Zhao;Mo-bin Cheng;Yu-wei Di;Hai-xia Yan;Chun-Yu Cao;Hui Dai;Ye Zhang
中科院分区：
文献类型：
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作者：
Niu Zhai;Zhong-liang Zhao;Mo-bin Cheng;Yu-wei Di;Hai-xia Yan;Chun-Yu Cao;Hui Dai;Ye Zhang
核糖体生物合成在真核细胞生长中至关重要，其中核糖体RNA前体的合成是第一步，也是限速步骤。在此，我们发现人类含PIH1结构域蛋白1（PIH1）可直接与组蛋白H4相互作用，并通过SNF5将Brg1 - SWI/SNF复合物招募至人类rRNA基因。这一过程可能参与了PIH1依赖的rRNA基因核心启动子处的DNase I超敏感染色质重塑。PIH1不仅介导Brg1复合物在核心启动子处的结合，还介导Pol I复合物在核心启动子处的结合，并增强rRNA基因的转录起始。此外，PIH1与H4K16之间的相互作用将沉默核仁重塑复合物（NoRC）的一个组分TIP5从核心区域排出，这表明PIH1参与了NoRC沉默的rRNA基因的去抑制过程。这些数据表明，PIH1是人类rRNA基因的正向调节因子，对于人类细胞从营养匮乏状态恢复以及在体内向葡萄糖诱导的指数增长转变极为重要。
Ribosome biogenesis is critical in the growth of eukaryotic cells, in which the synthesis of precursor ribosomal RNA is the first and rate-limiting step. Here, we show that human PIH1 domain-containing protein 1 (PIH1) interacts directly with histone H4 and recruits the Brg1-SWI/SNF complex via SNF5 to human rRNA genes. This process is likely involved in PIH1-dependent DNase I-hypersensitive chromatin remodeling at the core promoter of the rRNA genes. PIH1 mediates the occupancy of not only the Brg1 complex but also the Pol I complex at the core promoter and enhances transcription initiation of rRNA genes. Additionally, the interaction between PIH1 and H4K16 expels TIP5, a component of the silencing nucleolar remodeling complex (NoRC), from the core region, suggesting that PIH1 is involved in the derepression of NoRC-silenced rRNA genes. These data indicate that PIH1 is a positive regulator of human rRNA genes and is of great importance for the recovery of human cells from nutrient starvation and the transition to glucose-induced exponential growth in vivo.