Histone H3K27 methylation-mediated repression of Hairy regulates insect developmental transition by modulating ecdysone biosynthesis
Histone H3K27 methylation-mediated repression of Hairy regulates insect developmental transition by modulating ecdysone biosynthesis
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组蛋白 H3K27 甲基化介导的毛状抑制通过调节蜕皮激素生物合成来调节昆虫发育转变
DOI：
10.1073/pnas.2101442118
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Daojun Cheng
中科院分区：
文献类型：
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作者：
Yan Yang;Tujing Zhao;Zheng Li;Wenliang Qian;Jian Peng;Ling Wei;Dongqin Yuan;Yaoyao Li;Qingyou Xia;Daojun Cheng
昆虫的发育是由类固醇激素蜕皮激素和保幼激素（JH）共同协调的。多梳抑制复合物 2 (PRC2) 介导的组蛋白 H3K27 三甲基化 (H3K27me3) 在表观遗传上沉默基因转录，对于一系列生物过程至关重要，但 H3K27 甲基化在昆虫激素作用中的功能尚不清楚。在这里，我们证明 H3K27 甲基化介导的幼虫前胸腺 (PG) 毛转录的抑制是家蚕和果蝇蜕皮激素生物合成所必需的。 PG 中的 H3K27me3 水平在最后幼虫龄期间动态增加。通过 Bombyxor PG 特异性敲除果蝇中 PRC2 成分 Su(z)12 的抑制剂处理，PRC2 活性下调诱导 H3K27me3 减少，从而减少蜕皮激素生物合成并扰乱幼虫-蛹转变。从机制上讲，H3K27 甲基化以 JH 信号转导器 Hairy 为目标，抑制其在 PG 中的转录； Hairygene 的 PG 特异性敲除或过度表达会破坏蜕皮激素生物合成和发育转变；由 PG 特异性 Su(z)12 敲低引起的发育缺陷可以通过 Hairydown 调节部分挽救。将 JH 模拟物应用于 PG 会降低 H3K27me3 水平和 Su(z)12 表达。总而言之，我们的研究揭示了幼虫期PRC2介导的PG毛里的H3K27甲基化是蜕皮激素生物合成和幼虫-蛹转变所必需的，并为昆虫发育过程中JH和蜕皮激素之间串扰的表观遗传调控提供了见解。
Insect development is cooperatively orchestrated by the steroid hormone ecdysone and juvenile hormone (JH). The polycomb repressive complex 2 (PRC2)–mediated histone H3K27 trimethylation (H3K27me3) epigenetically silences gene transcription and is essential for a range of biological processes, but the functions of H3K27 methylation in insect hormone action are poorly understood. Here, we demonstrate that H3K27 methylation–mediated repression ofHairytranscription in the larval prothoracic gland (PG) is required for ecdysone biosynthesis inBombyxandDrosophila. H3K27me3 levels in the PG are dynamically increased during the last larval instar. H3K27me3 reduction induced by the down-regulation of PRC2 activity via inhibitor treatment inBombyxor PG-specific knockdown of the PRC2 componentSu(z)12inDrosophiladiminishes ecdysone biosynthesis and disturbs the larval–pupal transition. Mechanistically, H3K27 methylation targets the JH signal transducerHairyto repress its transcription in the PG; PG-specific knockdown or overexpression of theHairygene disrupts ecdysone biosynthesis and developmental transition; and developmental defects caused by PG-specificSu(z)12knockdown can be partially rescued byHairydown-regulation. The application of JH mimic to the PG decreases both H3K27me3 levels andSu(z)12expression. Altogether, our study reveals that PRC2-mediated H3K27 methylation atHairyin the PG during the larval period is required for ecdysone biosynthesis and the larval–pupal transition and provides insights into epigenetic regulation of the crosstalk between JH and ecdysone during insect development.