Ezh2 as an epigenetic checkpoint regulator during monocyte differentiation: a potential target to improve cardiac repair after myocardial infarction

Rondeaux, J.; Groussard, D.; Renet, S.; Tardif, V.; Dumesnil, A.; Chu, A.; Henry, J.-P.; Badji, Z.; Claire, V.; Beziau, D.; Guerrot, D.; Brand, M.; Richard, V.; Durand, E.; Brakenhielm, E.; Fraineau, S.

doi:10.1101/2021.02.17.428828

bioRxiv · 10.1101/2021.02.17.428828

Ezh2 as an epigenetic checkpoint regulator during monocyte differentiation: a potential target to improve cardiac repair after myocardial infarction

Rondeaux, J.·Groussard, D.·Renet, S.·Tardif, V.·Dumesnil, A.·Chu, A.·Henry, J.-P.·Badji, Z.·Claire, V.·Beziau, D.·Guerrot, D.·Brand, M.·Richard, V.·Durand, E.·Brakenhielm, E.·Fraineau, S.

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Abstract

Epigenetic regulation of histone H3K27 methylation has recently emerged as a key step during M2-like macrophage polarization, essential for cardiac repair after Myocardial Infarction (MI). We demonstrate for the first-time that EZH2, responsible for H3K27 methylation, has an ectopic cytoplasmic localization during monocyte differentiation in M2 macrophages. Moreover, we show that pharmacological EZH2 inhibition, with GSK-343, enhances bivalent genes, expression to promote human monocyte repair functions. 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.

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Rondeaux, J., Groussard, D., Renet, S., Tardif, V., Dumesnil, A., Chu, A., Henry, J.-P., Badji, Z., Claire, V., Beziau, D., Guerrot, D., Brand, M., Richard, V., Durand, E., Brakenhielm, E., Fraineau, S.. 2021-02-17. Ezh2 as an epigenetic checkpoint regulator during monocyte differentiation: a potential target to improve cardiac repair after myocardial infarction. https://doi.org/10.1101/2021.02.17.428828

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