DNA Replication Is Required for Circadian Clock Function by Regulating Rhythmic Nucleosome Composition.
DNA Replication Is Required for Circadian Clock Function by Regulating Rhythmic Nucleosome Composition.
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DOI：
10.1016/j.molcel.2017.05.029
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发表时间：
2017-07-20
期刊：
影响因子：
16
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Liu X;Dang Y;Matsu-Ura T;He Y;He Q;Hong CI;Liu Y
虽然生物钟和细胞周期之间的耦合允许生物钟在许多生物体中控制细胞分裂和DNA复制，但生物钟被认为独立于细胞周期发挥作用。在这里，我们表明，DNA复制所需的生物钟功能脉孢菌。DNA复制的遗传和药理学抑制通过抑制频率（frq）基因转录废除了显性和分子节律。frq启动子区核小体组成的节律性变化与DNA复制密切相关。已知参与组蛋白分解/重组的FACT复合物是时钟功能所需的，并以复制依赖性方式募集到frq启动子中，以促进组蛋白H2 A. Z被H2 A取代。最后，H2A.Z的缺失解除了生物钟对DNA复制的依赖。总之，这些结果建立了生物钟和细胞周期作为相互依赖的耦合振荡器，并确定DNA复制作为一个关键过程的昼夜节律机制。
Although the coupling between circadian and cell cycles allows circadian clocks to gate cell division and DNA replication in many organisms, circadian clocks were thought to function independently of cell cycle. Here we show that DNA replication is required for circadian clock function in Neurospora. Genetic and pharmacological inhibition of DNA replication abolished both overt and molecular rhythmicities by repressing frequency (frq) gene transcription. DNA replication is essential for the rhythmic changes of nucleosome composition at the frq promoter. The FACT complex, known to be involved in histone disassembly/reassembly, is required for clock function and is recruited to the frq promoter in a replication-dependent manner to promote replacement of histone H2A.Z by H2A. Finally, deletion of H2A.Z uncoupled the dependence of circadian clock on DNA replication. Together, these results establish circadian clock and cell cycle as interdependent coupled oscillators and identify DNA replication as a critical process in circadian mechanism.
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