Epigenetic regulator Stuxnet modulates octopamine effect on sleep through a Stuxnet-Polycomb-Octβ2R cascade

Epigenetic regulator Stuxnet modulates octopamine effect on sleep through a Stuxnet-Polycomb-Octβ2R cascade
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表观遗传调节器 Stuxnet 通过 Stuxnet-Polycomb-Octb2R 级联调节章鱼胺对睡眠的影响

DOI:
10.15252/embr.201947910
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发表时间:
2021-01-07
期刊:
影响因子:
7.7
通讯作者:
Du, Juan
Du, Juan
中科院分区:
生物学2区
文献类型:
--
作者:
Zhao, Zhangwu;Zhao, Xianguo;Du, Juan

文献摘要

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睡眠动态平衡对睡眠调节至关重要。表观遗传调控在睡眠动态平衡中的作用尚未确定。先前的研究表明,章鱼胺对睡眠稳态很重要。然而,章鱼在睡眠中接受的调节机制尚不清楚。在这项研究中,我们发现了一个表观遗传调控级联(Stuxnet-Polycomb-Oct beta 2R),它调节果蝇的章鱼胺受体。我们证明Stuxnet通过在成虫大脑椭圆形体内抑制Polycomb来正向调节Octβ2R,并且Oct beta 2R是介导章鱼胺在睡眠稳态中作用的主要受体之一。作为对章鱼胺的反应,Octβ2R转录因Stuxnet下调而被抑制。这种通过Stuxnet-Polycomb-OCT beta 2R级联的反馈对睡眠稳态调节至关重要。这项研究证明了一种Stuxnet-Polycomb-Oct beta 2R介导的章鱼胺接收的表观遗传调控机制,从而为睡眠稳态的表观遗传调控提供了一个例子。
Sleep homeostasis is crucial for sleep regulation. The role of epigenetic regulation in sleep homeostasis is unestablished. Previous studies showed that octopamine is important for sleep homeostasis. However, the regulatory mechanism of octopamine reception in sleep is unknown. In this study, we identify an epigenetic regulatory cascade (Stuxnet-Polycomb-Oct beta 2R) that modulates the octopamine receptor in Drosophila. We demonstrate that stuxnet positively regulates Oct beta 2R through repression of Polycomb in the ellipsoid body of the adult fly brain and that Oct beta 2R is one of the major receptors mediating octopamine function in sleep homeostasis. In response to octopamine, Oct beta 2R transcription is inhibited as a result of stuxnet downregulation. This feedback through the Stuxnet-Polycomb-Oct beta 2R cascade is crucial for sleep homeostasis regulation. This study demonstrates a Stuxnet-Polycomb-Oct beta 2R-mediated epigenetic regulatory mechanism for octopamine reception, thus providing an example of epigenetic regulation of sleep homeostasis.