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Updated: Jun 25, 2025

Induction and Validation of Cellular Senescence in Primary Human Cells
08:18

Induction and Validation of Cellular Senescence in Primary Human Cells

Published on: June 20, 2018

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Downregulation of Histone H3.3 Induces p53-Dependent Cellular Senescence in Human Diploid Fibroblasts

Yuki Yamamoto1, Ryou-U Takahashi1, Masaki Kinehara1

  • 1Department of Cellular and Molecular Biology, Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan.

Genes
|May 25, 2024
PubMed

Insights

Histone variant H3.3 downregulation triggers cellular senescence, characterized by growth arrest and specific molecular markers. This study reveals H3.3

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Epigenetics

Background:

  • Cellular senescence is a crucial tumor-suppressive mechanism involving irreversible growth arrest.
  • Histone modifications are key events in senescence, but the role of histone variant H3.3 remains unclear.

Purpose of the Study:

  • To investigate the function of histone variant H3.3 in cellular senescence.
  • To elucidate the molecular mechanisms underlying H3.3-regulated senescence.

Main Methods:

  • Depletion of H3.3 in cells.
  • Analysis of senescence-associated phenotypes (SAHF, SA-β-gal activity).
  • Investigation of the p53/p21 pathway and miR-22-3p regulation of H3F3B.

Main Results:

  • H3.3 downregulation induced growth suppression and senescence-like phenotypes.
  • H3.3 depletion activated the p53/p21-dependent pathway.
  • miR-22-3p was identified as an upstream regulator of H3F3B (encoding H3.3).

Conclusions:

  • H3.3 abundance plays a critical role in regulating cellular senescence.
  • H3.3 acts through the p53/p21 pathway and is regulated by miR-22-3p.
  • H3.3 is a potential therapeutic target for cancer treatment.
Keywords:
aginghistonemicroRNAp53senescence

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