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Updated: Aug 27, 2025

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Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence

Sergio Rodríguez1, Litzy Gisella Bermúdez1, Daniel González1

  • 1Institute of Human Genetics, School of Medicine, Pontificia Universidad Javeriana, Bogotá 110231, Colombia.

Molecular Medicine Reports
|September 28, 2022
PubMed

Insights

Cellular senescence involves cell cycle arrest regulated by p16INK4A. This study reveals histone acetylation, particularly H3K18Ac, and SIRT7 are critical epigenetic regulators of p16INK4A gene expression during senescence.

Area of Science:

  • Epigenetics
  • Cellular Biology
  • Molecular Biology

Background:

  • Cell senescence is a state of irreversible cell cycle arrest.
  • p16INK4A (CDKN2A) is a key regulator of senescence, controlled by epigenetic mechanisms.
  • Sirtuins (SIRTs) are NAD+-dependent deacetylases involved in aging and disease.

Purpose of the Study:

  • To investigate the role of histone acetylation and SIRT7 in regulating CDKN2A/p16 gene expression during cellular senescence.
  • To elucidate the epigenetic mechanisms underlying senescence.

Main Methods:

  • Quantitative PCR
  • Western blot
  • Chromatin immunoprecipitation (ChIP)
  • siRNAs assays
  • MRC5 cell culture

Main Results:

  • Senescence in MRC5 cells correlated with increased H3K9Ac and H3K18Ac enrichment and CDKN2A/p16 overexpression.
  • SIRT7 knockdown in senescent cells led to H3K18Ac presence and CDKN2A/p16 promoter activation.
  • These findings indicate SIRT7's role in the epigenetic regulation of p16INK4A during senescence.

Conclusions:

  • SIRT7 acts as a crucial epigenetic regulator in p16INK4A-mediated cellular senescence.
  • Histone acetylation patterns, specifically H3K18Ac, are dynamically regulated during senescence.
  • Epigenetic modifications provide a mechanism for controlling cell cycle arrest.
Keywords:
agingcyclin‑dependent kinase inhibitor 2A/p16epigeneticssenescencesirtuin 7

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