Escape from oncogene-induced senescence is controlled by POU2F2 and memorized by chromatin scars - Archive ouverte HAL
Article Dans Une Revue Cell Genomics Année : 2023

Escape from oncogene-induced senescence is controlled by POU2F2 and memorized by chromatin scars

Résumé

Although oncogene-induced senescence (OIS) is a potent tumor-suppressor mechanism, recent studies revealed that cells could escape from OIS with features of transformed cells. However, the mechanisms that promote OIS escape remain unclear, and evidence of post-senescent cells in human cancers is missing. Here, we unravel the regulatory mechanisms underlying OIS escape using dynamic multidimensional profiling. We demonstrate a critical role for AP1 and POU2F2 transcription factors in escape from OIS and identify senescence-associated chromatin scars (SACSs) as an epigenetic memory of OIS detectable during colorectal cancer progression. POU2F2 levels are already elevated in precancerous lesions and as cells escape from OIS, and its expression and binding activity to cis-regulatory elements are associated with decreased patient survival. Our results support a model in which POU2F2 exploits a precoded enhancer landscape necessary for senescence escape and reveal POU2F2 and SACS gene signatures as valuable biomarkers with diagnostic and prognostic potential.
Fichier principal
Vignette du fichier
Ivá N Martínez-Zamudio et al. - 2023 - Escape from oncogene-induced senescence is controlled by POU2F2 and memorized by chromatin scar-annotated.pdf (6.01 Mo) Télécharger le fichier
Origine Fichiers produits par l'(les) auteur(s)
Licence

Dates et versions

hal-04201593 , version 1 (05-10-2022)
hal-04201593 , version 2 (10-09-2023)

Licence

Identifiants

Citer

Ricardo Iván Martínez-Zamudio, Alketa Stefa, José Américo Nabuco Leva Ferreira Freitas, Themistoklis Vasilopoulos, Mark Simpson, et al.. Escape from oncogene-induced senescence is controlled by POU2F2 and memorized by chromatin scars. Cell Genomics, 2023, 3 (4), pp.100293. ⟨10.1016/j.xgen.2023.100293⟩. ⟨hal-04201593v2⟩
110 Consultations
77 Téléchargements

Altmetric

Partager

More