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Related Concept Videos

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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The circadian—or biological—clock is an intrinsic, timekeeping, molecular mechanism that allows plants to coordinate physiological activities over 24-hour cycles called circadian rhythms. Photoperiodism is a collective term for the biological responses of plants to variations in the relative lengths of dark and light periods. The period of light-exposure is called the photoperiod.
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Heterochromatin02:38

Heterochromatin

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The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
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Spreading of Chromatin Modifications02:25

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The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
Writers
The writer...
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Euchromatin01:01

Euchromatin

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The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
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Histone Modification02:32

Histone Modification

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The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
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Updated: Sep 8, 2025

Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters
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Circadian clock function does not require the histone methyltransferase MLL3.

Matthew Baxter1,2, Toryn Poolman1,2, Peter Cunningham3

  • 1NIHR Oxford Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|June 15, 2022
PubMed
Summary
This summary is machine-generated.

Histone methyltransferase MLL3 is not essential for core circadian clock function or behavioral rhythms in mice. Its catalytic activity is dispensable for maintaining circadian oscillations, though it may influence inflammatory responses.

Keywords:
KMT2CMLL3circadianclockepigeneticshistoneinflammationmethyltransferase

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Area of Science:

  • Chronobiology
  • Epigenetics
  • Molecular Biology

Background:

  • The circadian clock regulates gene expression temporally via transcription-translation feedback loops.
  • Epigenetic regulators, including histone methyltransferases like MLL3, are recruited to control gene expression.
  • MLL3 was previously suggested to be crucial for circadian oscillations in cell cultures.

Purpose of the Study:

  • To investigate the role of MLL3's methyltransferase activity in circadian organization in whole animals.
  • To determine if MLL3 is required for circadian oscillations in vitro and behavioral rhythms in vivo.

Main Methods:

  • Utilized mice expressing catalytically inactive MLL3.
  • Assessed circadian oscillations in various tissues in vitro.
  • Monitored circadian behavioral rhythms in vivo.
  • Analyzed global H3K4 methylation levels and H3K4me3/H3K4me1 mark repositioning in the liver.
  • Evaluated circadian output functions, including the regulation of inflammation.

Main Results:

  • MLL3 methyltransferase activity is not required for circadian oscillations in vitro or behavioral rhythms in vivo.
  • Loss of MLL3-dependent methylation did not alter global H3K4 methylation in the liver, indicating compensatory mechanisms.
  • Observed repositioning of H3K4me1 marks but no significant changes in abundance around core circadian clock genes.
  • Circadian control of inflammation was largely preserved, with some sexually dimorphic changes in cytokine regulation.

Conclusions:

  • MLL3-directed histone methylation is not essential for the core circadian clock mechanism.
  • MLL3 activity may play a role in modulating specific circadian output pathways, particularly the inflammatory response.