Ezh2 emerges as an epigenetic checkpoint regulator during monocyte differentiation limiting cardiac dysfunction post-MI - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2023

Ezh2 emerges as an epigenetic checkpoint regulator during monocyte differentiation limiting cardiac dysfunction post-MI

Zina Badji
  • Function : Author
Claire Vézier
  • Function : Author

Abstract

Abstract Epigenetic regulation of histone H3K27 methylation has recently emerged as a key step during alternative immunoregulatory M2-like macrophage polarization; known to impact cardiac repair after Myocardial Infarction (MI). We hypothesized that EZH2, responsible for H3K27 methylation, could act as an epigenetic checkpoint regulator during this process. We demonstrate for the first time an ectopic EZH2, and putative, cytoplasmic inactive localization of the epigenetic enzyme, during monocyte differentiation into M2 macrophages in vitro as well as in immunomodulatory cardiac macrophages in vivo in the post-MI acute inflammatory phase. Moreover, we show that pharmacological EZH2 inhibition, with GSK-343, resolves H3K27 methylation of bivalent gene promoters, thus enhancing their expression to promote human monocyte repair functions. In line with this protective effect, GSK-343 treatment accelerated cardiac inflammatory resolution preventing infarct expansion and subsequent cardiac dysfunction in female mice post-MI in vivo. In conclusion, our study reveals that pharmacological epigenetic modulation of cardiac-infiltrating immune cells may hold promise to limit adverse cardiac remodeling after MI.
Fichier principal
Vignette du fichier
Rondeaux_et_al-2023-Nature_Communications.pdf (5.23 Mo) Télécharger le fichier
Origin Publisher files allowed on an open archive

Dates and versions

hal-04190661 , version 1 (29-08-2023)

Identifiers

Cite

Julie Rondeaux, Déborah Groussard, Sylvanie Renet, Virginie Tardif, Anaïs Dumesnil, et al.. Ezh2 emerges as an epigenetic checkpoint regulator during monocyte differentiation limiting cardiac dysfunction post-MI. Nature Communications, 2023, 14 (1), pp.4461. ⟨10.1038/s41467-023-40186-0⟩. ⟨hal-04190661⟩
54 View
27 Download

Altmetric

Share

Gmail Mastodon Facebook X LinkedIn More