Open Access

Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence

  • Authors:
    • Sergio Rodríguez
    • Litzy Gisella Bermúdez
    • Daniel González
    • Camila Bernal
    • Alejandra Cañas
    • Teresa Morales-Ruíz
    • Berta Henríquez
    • Adriana Rojas
  • View Affiliations

  • Published online on: September 27, 2022     https://doi.org/10.3892/mmr.2022.12861
  • Article Number: 345
  • Copyright: © Rodríguez et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cell senescence is a state of limited cell proliferation during a stress response or as part of a programmed process. When a senescent cell stops dividing, maintaining metabolic activity contributes to cellular homeostasis maintenance. In this process, the cell cycle is arrested at the G0/G1 phase. p16INK4A protein is a key regulator of this process via its cyclin‑dependent kinase inhibitor (CDKI) function. CDKI 2A (CDKN2A)/p16 gene expression is regulated by DNA methylation and histone acetylation. Sirtuins (SIRTs) are nicotinamide dinucleotide (NAD+)‑dependent deacetylases that have properties which prevent diseases and reverse certain aspects of aging (such as immune, metabolic and cardiovascular diseases). By performing quantitative PCR, Western blot, ChIP, and siRNAs assays, in this study it was demonstrated that CDKN2A/p16 gene transcriptional activation and repression were accompanied by selective deposition and elimination of histone acetylation during the senescence of MRC5 cells. Specifically, significant H3K9Ac and H3K18Ac enrichment in cells with a senescent phenotype concomitant with CDKN2A/p16 gene overexpression was demonstrated compared with the non‑senescent phenotype. Furthermore, the presence of H3K18Ac in deacetyl‑transferase SIRT7 knockdown MRC5 cells allowed CDKN2A/p16 promoter activation. These results suggested that SIRT7 served as a critical component of an epigenetic mechanism involved in senescence mediated by the CDKN2A/p16 gene.
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November-2022
Volume 26 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Rodríguez S, Bermúdez LG, González D, Bernal C, Cañas A, Morales-Ruíz T, Henríquez B and Rojas A: Transcriptional regulation of <em>CDKN2A/p16</em> by sirtuin 7 in senescence. Mol Med Rep 26: 345, 2022
APA
Rodríguez, S., Bermúdez, L.G., González, D., Bernal, C., Cañas, A., Morales-Ruíz, T. ... Rojas, A. (2022). Transcriptional regulation of <em>CDKN2A/p16</em> by sirtuin 7 in senescence. Molecular Medicine Reports, 26, 345. https://doi.org/10.3892/mmr.2022.12861
MLA
Rodríguez, S., Bermúdez, L. G., González, D., Bernal, C., Cañas, A., Morales-Ruíz, T., Henríquez, B., Rojas, A."Transcriptional regulation of <em>CDKN2A/p16</em> by sirtuin 7 in senescence". Molecular Medicine Reports 26.5 (2022): 345.
Chicago
Rodríguez, S., Bermúdez, L. G., González, D., Bernal, C., Cañas, A., Morales-Ruíz, T., Henríquez, B., Rojas, A."Transcriptional regulation of <em>CDKN2A/p16</em> by sirtuin 7 in senescence". Molecular Medicine Reports 26, no. 5 (2022): 345. https://doi.org/10.3892/mmr.2022.12861