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DOI	10.1073/pnas.2019756118
	Clock proteins regulate spatiotemporal organization of clock genes to control circadian rhythms
	Xiao Y.; Yuan Y.; Jimenez M.; Soni N.; Yadlapalli S.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:28
英文摘要	Circadian clocks regulate ∼24-h oscillations in gene expression, behavior, and physiology. While the genetic and molecular mechanisms of circadian rhythms are well characterized, what remains poorly understood are the intracellular dynamics of circadian clock components and how they affect circadian rhythms. Here, we elucidate how spatiotemporal organization and dynamics of core clock proteins and genes affect circadian rhythms in Drosophila clock neurons. Using high-resolution imaging and DNA-fluorescence in situ hybridization techniques, we demonstrate that Drosophila clock proteins (PERIOD and CLOCK) are organized into a few discrete foci at the nuclear envelope during the circadian repression phase and play an important role in the subnuclear localization of core clock genes to control circadian rhythms. Specifically, we show that core clock genes, period and timeless, are positioned close to the nuclear periphery by the PERIOD protein specifically during the repression phase, suggesting that subnuclear localization of core clock genes might play a key role in their rhythmic gene expression. Finally, we show that loss of Lamin B receptor, a nuclear envelope protein, leads to disruption of PER foci and per gene peripheral localization and results in circadian rhythm defects. These results demonstrate that clock proteins play a hitherto unexpected role in the subnuclear reorganization of core clock genes to control circadian rhythms, revealing how clocks function at the subcellular level. Our results further suggest that clock protein foci might regulate dynamic clustering and spatial reorganization of clock-regulated genes over the repression phase to control circadian rhythms in behavior and physiology. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Circadian rhythms; Live imaging; Nuclear organization
语种	英语
scopus关键词	DNA; transcription factor; transcription factor CLOCK; cell receptor; circadian rhythm signaling protein; Clk protein, Drosophila; Drosophila protein; lamin B receptor; PER protein, Drosophila; transcription factor CLOCK; Article; cell nucleus membrane; circadian rhythm; controlled study; Drosophila melanogaster; gene control; gene expression; genetic transcription; high resolution computer tomography; in situ hybridization; in vitro study; molecular mechanics; nonhuman; protein degradation; RNA translation; spatiotemporal analysis; animal; cell nucleus; circadian rhythm; gene expression regulation; genetics; metabolism; physiology; time factor; time lapse imaging; Animals; Cell Nucleus; Circadian Clocks; Circadian Rhythm; CLOCK Proteins; Drosophila melanogaster; Drosophila Proteins; Gene Expression Regulation; Period Circadian Proteins; Receptors, Cytoplasmic and Nuclear; Time Factors; Time-Lapse Imaging
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251132
作者单位	Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, United States; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, United States
推荐引用方式 GB/T 7714	Xiao Y.,Yuan Y.,Jimenez M.,et al. Clock proteins regulate spatiotemporal organization of clock genes to control circadian rhythms[J],2021,118(28).
APA	Xiao Y.,Yuan Y.,Jimenez M.,Soni N.,&Yadlapalli S..(2021).Clock proteins regulate spatiotemporal organization of clock genes to control circadian rhythms.Proceedings of the National Academy of Sciences of the United States of America,118(28).
MLA	Xiao Y.,et al."Clock proteins regulate spatiotemporal organization of clock genes to control circadian rhythms".Proceedings of the National Academy of Sciences of the United States of America 118.28(2021).