遗传 ›› 2017, Vol. 39 ›› Issue (12): 1122-1137.doi: 10.16288/j.yczz.17-350

• 特邀综述 • 上一篇    下一篇

哺乳动物生物钟的遗传和表观遗传研究进展

岳敏1,2(),杨禹1,郭改丽1,秦曦明1()   

  1. 1. 安徽大学健康科学研究院,合肥 230601
    2. 安徽大学生命科学学院,合肥 230601
  • 收稿日期:2017-10-27 修回日期:2017-11-16 出版日期:2017-12-20 发布日期:2017-12-20
  • 作者简介:岳敏,本科,专业方向：生物科学。E-mail: yuemin_ahu@163.com|秦曦明，博士，教授，博士生导师，研究方向：生物钟分子组分的功能及其相互作用参与生物钟调控的分子机制。E-mail: qin.ximing@ahu.edu.cn|秦曦明教授,2010年从美国Vanderbilt大学获得博士学位,现任职于安徽大学健康科学研究院。课题组主要研究方向是生物钟(近日节律)的分子与结构基础、生物钟组分的功能和生物钟调节健康的靶点分子的研究。曾经利用蓝绿细菌作为模式生物,阐述核心振荡器和次级振荡器之间的联系与相互作用,并提出真核生物可能存在不依赖转录翻译环路的核心分子振荡器的假设。通过研究生物钟蛋白分子的相互作用,解析生物钟如何维持稳定的相关机制。相关的研究成果发表在Nature、Proc Natl Acad Sci USA、PLoS Biology、Current Biology、J Biol Rhythms等学术期刊上。目前主持国家自然科学基金面上项目与安徽省自然科学基金项目。
  • 基金资助:
    国家自然科学基金项目(31571208);安徽省自然科学基金项目(1608085MH212);安徽大学大学生科研训练计划项目(J10118520418)

Genetic and epigeneticregulations of mammalian circadian rhythms

Yue Min1,2(),Yang Yu1,Guo Gaili1,Qin Ximing1()   

  1. 1. Institute of Health Sciences, Anhui University, Hefei 230601, China
    2. School of Life Sciences, Anhui University, Hefei 230601, China
  • Received:2017-10-27 Revised:2017-11-16 Online:2017-12-20 Published:2017-12-20
  • Supported by:
    the National Natural Science Foundation of China(31571208);the Natural Science Foundation of Anhui Province(1608085MH212);Anhui University Undergraduate Student Training Grant(J10118520418)

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摘要：

生物钟对生物机体的生存与环境适应具有着重要意义,其相关研究近年来受到人们的广泛关注。生物钟的重要性质之一是内源节律的周期性,当前的研究认为这种周期性是由生物钟相关基因转录翻译的多反馈环路构成核心机制调控着近似24 h的节律振荡。哺乳动物的生物钟系统存在一个多层次的结构,包括位于视交叉上核的主时钟和外周器官和组织的子时钟。虽然主时钟和子时钟存在的组织不同,但是参与调节生物钟的分子机制是一致的。近年来,通过正向、反向遗传学方法和表观遗传学的研究方法,对生物钟的分子机制的解析和认知愈发深入。本文在简单回顾生物钟基因发现历史的基础上,重点从遗传学和表观遗传学两个方面,从振荡周期的角度,对哺乳动物生物钟分子机制的研究进展进行了综述性介绍,以期为靶向调节生物钟来改善机体的稳态系统的研究提供参考,同时希望能促进时间生物学领域与更多其他领域形成交叉研究。

关键词: 生物钟, 近日节律, 生物钟基因, 转录翻译反馈环路, 顺式作用元件, 转录因子, 表观遗传学

Abstract:

The circadian clocks are vital to many organisms for their survival and adaption to the surrounding environment. More and more people are interested in the circadian clock and related researches. One of the key characteristics of this endogenous clock is its periodicity. Mechanisms underlying the mammalian circadian rhythms with ~24 h periodicity involve interlocked transcriptional and translational feedback loops. The circadian clock system in mammals consists of hierarchical structures, with the suprachiasmatic nucleus (SCN) as the central pacemaker and peripheral oscillators in other organs. In spite of the central and peripheral oscillators, the molecular mechanisms are the same within the SCN and peripheral organs. In the past decades, major achievements are accomplished by using forward and reverse genetics, as well as epigenetic approaches. In this review, we recapitulate the history of how clock-related genes were identified, and summarize the main achievements in genetics and epigenetics to understand the molecular underpinnings. We hope it can offer basic knowledge for further researches, a reference for experimental designs aiming to adjust organisms’ homeostasis by modulating the clock, and provide a foundation to build interdisciplinary research networks.

Key words: Circadian clock, circadian rhythm, clock genes, transcriptional and translational feedback loop, cis-regulating elements, transcription factors, epigenetics