Publication:
Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence.

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Date

2022-08-17

Authors

Rodriguez, Sergio
Bermudez, Litzy Gisella
Gonzalez, Daniel
Bernal, Camila
Cañas, Alejandra
Morales-Ruiz, Teresa
Henriquez, Berta
Rojas, Adriana

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Spandidos Publications
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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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MeSH Terms

Cellular senescence
Cyclin-dependent kinase inhibitor p16
Cyclin-dependent kinases
Histones
NAD
Niacinamide
Sirtuins

DeCS Terms

Histonas
Inhibidor p16 de la quinasa dependiente de ciclina
Niacinamida
Quinasas ciclina-dependientes
Senescencia celular
Sirtuinas

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Keywords

Aging, Cyclin‑dependent kinase inhibitor 2A/p16, Epigenetics, Senescence, Sirtuin 7

Citation

Rodríguez S, Bermúdez LG, González D, Bernal C, Cañas A, Morales-Ruíz T, et al. Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence. Mol Med Rep. 2022 Nov;26(5):345