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Gene Expression by RNA-Seq of Peripheral Blood Monocyte with the EZH2 inhibitor GSK-343

ABSTRACT: Epigenetic regulation of histone H3K27 methylation has recently emerged as a key step during alternative M2-like macrophage (M2) polarization, essential for 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 inactivation of EZH2 activity, linked to ectopic cytoplasmic localization of the epigenetic enzyme, during monocyte differentiation in vitro as well as in M2 macrophages in vivo during post-MI cardiac inflammation. Moreover, we show that pharmacological EZH2 inhibition, with GSK-343, resolves H3K27 methylation at the promoter of bivalent genes, 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 after MI in vivo. In conclusion, our study reveals that epigenetic modulation of cardiac-infiltrating immune cells may hold promise to limit adverse cardiac remodeling after MI.

ORGANISM(S): Homo sapiens

PROVIDER: GSE165543 | GEO | 2023/04/24

REPOSITORIES: GEO

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