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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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Nucleosome proteostasis and histone turnover.

Adrian Arrieta1, Thomas M Vondriska1,2,3

  • 1Departments of Anesthesiology and Perioperative Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.

Frontiers in Molecular Biosciences
|October 17, 2022
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Summary

Maintaining protein homeostasis (proteostasis) is vital for cell survival and function. This review highlights how nucleosome proteostasis, crucial for chromatin organization, impacts cell health and disease.

Keywords:
chaperonechromatindevelopmentdiseasefoldinghistonenucleosome

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Area of Science:

  • Molecular Biology
  • Cell Biology
  • Epigenetics

Background:

  • Protein folding homeostasis (proteostasis) is essential for cellular survival and function.
  • Cell type specification relies on chromatin organization, which is influenced by nucleosome dynamics.
  • Disrupted chromatin organization can lead to severe cellular consequences.

Purpose of the Study:

  • To emphasize the critical role of nucleosome proteostasis in maintaining chromatin organization.
  • To explain the involvement of histone chaperones and ATP-dependent chromatin remodelers in nucleosome proteostasis.
  • To outline mechanisms of disrupted nucleosome proteostasis in disease and its link to the unfolded protein response.

Main Methods:

  • This is a review article, synthesizing existing research.
  • Literature review on nucleosome dynamics, chromatin organization, and proteostasis.
  • Analysis of mechanisms linking histone turnover, nucleosome proteostasis, and disease.

Main Results:

  • Nucleosome proteostasis is fundamental for proper chromatin organization and cell function.
  • Histone chaperones and ATP-dependent chromatin remodelers are key mediators of nucleosome proteostasis.
  • Disruptions in nucleosome proteostasis are implicated in various diseases.
  • Histone turnover mechanisms may interact with unfolded protein response pathways.

Conclusions:

  • Nucleosome proteostasis is critical for maintaining cellular health and function.
  • Dysregulation of nucleosome proteostasis contributes to disease pathogenesis.
  • Understanding these mechanisms offers potential therapeutic targets.