Ezh2 promotes clock function and hematopoiesis independent of histone methyltransferase activity in zebrafish.
Ezh2 promotes clock function and hematopoiesis independent of histone methyltransferase activity in zebrafish.
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Ezh2 促进斑马鱼的时钟功能和造血功能，与组蛋白甲基转移酶活性无关
DOI：
10.1093/nar/gky101
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发表时间：
2018-04-20
影响因子：
14.9
通讯作者：
Wang H
中科院分区：
文献类型：
--
作者：
Zhong Y;Ye Q;Chen C;Wang M;Wang H
EZH2是多梳抑制复合体2(PRC2)的一个亚基，通过H3K27me3沉默基因转录，并通过基因沉默对哺乳动物肝脏的昼夜节律调节和造血起重要作用。然而，人们对Ezh2在活斑马鱼中的作用知之甚少。在这里，我们发现斑马鱼EZH2通过E-box和RORE基序直接受到生物钟的调节，而核心生物钟基因per1a、per1b、xi1aa和xi1ab在EZH2缺失突变体和EZH2变异斑马鱼中下调，并且EZH2的敲除或过表达改变了运动节律，表明Ezh2是斑马鱼昼夜节律调节所必需的。与其典型的沉默功能相反，斑马鱼Ezh2通过直接与关键的生物钟蛋白结合来上调这些关键的生物钟基因，而不依赖于组蛋白甲基转移酶的活性。同样，Ezh2通过增强cmyb和lck等造血基因的表达而促进造血。总之，我们的发现第一次证明了Ezh2在昼夜节律调节和造血方面的作用不依赖于沉默PRC2。
EZH2 is a subunit of polycomb repressive complex 2 (PRC2) that silences gene transcription via H3K27me3 and was shown to be essential for mammalian liver circadian regulation and hematopoiesis through gene silencing. Much less, however, is known about how Ezh2 acts in live zebrafish. Here, we show that zebrafish ezh2 is regulated directly by the circadian clock via both E-box and RORE motif, while core circadian clock genes per1a, per1b, cry1aa and cry1ab are down-regulated in ezh2 null mutant and ezh2 morphant zebrafish, and either knockdown or overexpression of ezh2 alters locomotor rhythms, indicating that Ezh2 is required for zebrafish circadian regulation. In contrast to its canonical silencing function, zebrafish Ezh2 up-regulates these key circadian clock genes independent of histone methyltransferase activity by directly binding to key circadian clock proteins. Similarly, Ezh2 contributes to hematopoiesis by enhancing expression of hematopoietic genes such as cmyb and lck. Together, our findings demonstrate for the first time that Ezh2 acts in both circadian regulation and hematopoiesis independent of silencing PRC2.
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