SETD4 Regulates Cell Quiescence and Catalyzes the Trimethylation of H4K20 during Diapause Formation in Artemia
SETD4 Regulates Cell Quiescence and Catalyzes the Trimethylation of H4K20 during Diapause Formation in Artemia
复制标题
SETD4 在丰年虫滞育形成过程中调节细胞静止并催化 H4K20 三甲基化
DOI：
10.1128/mcb.00453-16
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发表时间：
2017-04-01
影响因子：
5.3
通讯作者：
Yang, Wei-Jun
中科院分区：
文献类型：
--
作者：
Dai, Li;Ye, Sen;Yang, Wei-Jun
细胞静止作为细胞生命的一个重要特征，对细胞的正常发育、再生和抗逆能力有重要作用，并可能在某些退行性疾病中发挥作用。然而，静止背后的机制在很大程度上仍然未知。卤虫的包囊胚胎对于研究这种状态的调节是有用的，因为它们在滞育（一种专性休眠状态）期间保持长时间的静止。在本研究中，SET结构域的蛋白4，组蛋白赖氨酸甲基转移酶从卤虫，被确定，其特征在于，并命名为Ar-SETD 4。我们发现Ar-SETD 4在处于静止状态的卤虫滞育胚胎中大量表达。三甲基化组蛋白H4 K20（H4 K20 me 3）在滞育胚胎中富集。Ar-SET 4的敲除显着降低了H4 K20 me 3的水平，并阻止了滞育胚胎的形成，其中细胞周期和胚胎发生都没有停止。通过体外组蛋白甲基转移酶（HMT）测定和细胞系中的过表达证实Ar-SETD 4对H4 K20 me 3的催化活性。本研究为深入了解SETD 4的功能和细胞静止调节机制提供了新的思路。
ABSTRACT 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 Artemia 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 Artemia, was identified, characterized, and named Ar-SETD4. We found that Ar-SETD4 was expressed abundantly in Artemia 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 in vitro 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.