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Related Concept Videos

Circadian Rhythms and Gene Regulation02:19

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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 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.
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Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
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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.
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Chromatin immunoprecipitation, or ChIP, is an antibody-based technique used to identify sites on DNA that bind to transcription factors of interest or histone proteins. It also helps determine the type of histone modifications such as acetylation, phosphorylation, or methylation.
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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters
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ATAC-clock: An aging clock based on chromatin accessibility.

Francesco Morandini1, Cheyenne Rechsteiner1, Kevin Perez2

  • 1Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.

Geroscience
|November 4, 2023
PubMed
Summary
This summary is machine-generated.

Researchers developed a new epigenetic aging clock using chromatin accessibility, which accurately predicts age and links to gene expression changes. This chromatin accessibility clock outperforms transcriptomic clocks for age prediction.

Keywords:
ATAC sequencingAgingBiomarkerChromatin accessibilityEpigenetic clock

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Area of Science:

  • Epigenetics
  • Genomics
  • Aging Research

Background:

  • Aging clocks based on DNA methylation are established but have interpretability issues.
  • The potential of other epigenetic features for age prediction remains largely unexplored.
  • Previous DNA methylation clocks show limited correlation with gene expression, questioning their biological relevance.

Purpose of the Study:

  • To investigate chromatin accessibility as a basis for novel epigenetic aging clocks.
  • To assess the relationship between chromatin accessibility changes and gene expression during aging.
  • To compare the performance of a chromatin accessibility clock against a transcriptomic clock.

Main Methods:

  • Collected blood samples from 159 human donors.
  • Generated data on chromatin accessibility, transcriptomics, and cell composition.
  • Constructed an aging clock model using chromatin accessibility features.

Main Results:

  • Developed a novel chromatin accessibility-based aging clock with a median absolute error of 5.27 years.
  • Observed strong correlations between chromatin accessibility changes and transcriptomic alterations.
  • Demonstrated that the chromatin accessibility clock significantly outperforms a matched transcriptomic clock.

Conclusions:

  • Epigenetic aging clocks can be effectively constructed using chromatin accessibility.
  • Chromatin accessibility alterations are cell-intrinsic and directly linked to transcriptional changes.
  • This approach offers a more interpretable and accurate method for epigenetic age prediction compared to transcriptomic clocks.