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Circadian Rhythms and Gene Regulation02:19

Circadian Rhythms and Gene Regulation

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The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent...
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Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
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The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
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Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
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In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells
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Nuclear envelope protein MAN1 regulates clock through BMAL1.

Shu-Ting Lin1, Luoying Zhang1, Xiaoyan Lin1

  • 1Department of Neurology, University of California, San Francisco, San Francisco, United States.

Elife
|September 4, 2014
PubMed
Summary

The inner nuclear membrane protein MAN1 enhances the transcription of the core circadian clock component BMAL1. This discovery links the nuclear envelope to circadian rhythm regulation, impacting bodily functions.

Keywords:
BMAL1MAN1circadian rhythmnuclear envelope

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Area of Science:

  • Chronobiology
  • Molecular Biology
  • Cell Biology

Background:

  • Circadian clocks are internal pacemakers regulating homeostatic processes via feedback loops.
  • The nuclear envelope is a known gene regulatory machine, but its role in circadian rhythms is unexplored.

Purpose of the Study:

  • To investigate the role of the nuclear envelope in circadian clock regulation.
  • To identify novel components and pathways involved in maintaining circadian rhythmicity.

Main Methods:

  • Investigated the interaction between the inner nuclear membrane protein MAN1 and the core clock component BMAL1.
  • Analyzed the effect of MAN1 on BMAL1 gene transcription.

Main Results:

  • The inner nuclear membrane protein MAN1 positively modulates the transcription of BMAL1.
  • MAN1 directly binds to the BMAL1 promoter, enhancing its transcriptional activity.

Conclusions:

  • Established a novel connection between the nuclear periphery and circadian rhythmicity.
  • Demonstrated that MAN1 is a key regulator of the core circadian clock component BMAL1.
  • Bridged two global regulatory systems: the nuclear envelope and circadian rhythms.