Dai Li, Ye Sen, Li Hua-Wei, Chen Dian-Fu, Wang Hong-Liang, Jia Sheng-Nan, Lin Cheng, Yang Jin-Shu, Yang Fan, Nagasawa Hiromichi, Yang Wei-Jun
College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Mol Cell Biol. 2017 Mar 17;37(7). doi: 10.1128/MCB.00453-16. Print 2017 Apr 1.
As a prominent characteristic of cell life, the regulation of cell quiescence is important for proper development, regeneration, and stress resistance and may play a role in certain degenerative diseases. However, the mechanism underlying quiescence remains largely unknown. Encysted embryos of are useful for studying the regulation of this state because they remain quiescent for prolonged periods during diapause, a state of obligate dormancy. In the present study, SET domain-containing protein 4, a histone lysine methyltransferase from , was identified, characterized, and named Ar-SETD4. We found that Ar-SETD4 was expressed abundantly in diapause embryos, in which cells were in a quiescent state. Meanwhile, trimethylated histone H4K20 (H4K20me3) was enriched in diapause embryos. The knockdown of Ar-SETD4 reduced the level of H4K20me3 significantly and prevented the formation of diapause embryos in which neither the cell cycle nor embryogenesis ceased. The catalytic activity of Ar-SETD4 on H4K20me3 was confirmed by an histone methyltransferase (HMT) assay and overexpression in cell lines. This study provides insights into the function of SETD4 and the mechanism of cell quiescence regulation.
作为细胞生命的一个显著特征，细胞静止的调控对于正常发育、再生和抗逆性很重要，并且可能在某些退行性疾病中发挥作用。然而，静止状态背后的机制在很大程度上仍然未知。秀丽隐杆线虫的滞育胚胎对于研究这种状态的调控很有用，因为它们在滞育期间（一种 obligate 休眠状态）会长时间保持静止。在本研究中，从秀丽隐杆线虫中鉴定、表征并命名了含 SET 结构域蛋白 4（一种组蛋白赖氨酸甲基转移酶），将其命名为 Ar-SETD4。我们发现 Ar-SETD4 在秀丽隐杆线虫滞育胚胎中大量表达，其中细胞处于静止状态。同时，三甲基化组蛋白 H4K20（H4K20me3）在滞育胚胎中富集。敲低 Ar-SETD4 显著降低了 H4K20me3 的水平，并阻止了滞育胚胎的形成，在这种胚胎中细胞周期和胚胎发育均未停止。通过组蛋白甲基转移酶（HMT）测定和在细胞系中的过表达证实了 Ar-SETD4 对 H4K20me3 的催化活性。本研究为 SETD4 的功能和细胞静止调控机制提供了见解。
