The role of methyltransferase, Set7/9 in islet inflammation

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Set7/9 is an enzyme that methylates lysine 4 on histone 3 (H3K4) to maintain euchromatin architecture. While Set7/9 contributes to the transactivation of beta cell specific genes, Set7/9 also reportedly binds NF-kB, thus regulating inflammatory genes in non-beta cells. Given that inflammation is a component of beta cell dysfunction in diabetes, the aim of this study was to elucidate the role of Set7/9 on proinflammatory cytokine signaling in beta cells. To induce inflammation, mouse insulinoma cells were treated with a cocktail of pro-inflammatory cytokines. Cytokine treatment induced the expression of iNOS, which was attenuated by the Set7/9 knockdown. Set7/9 knockdown attenuated cytokine-induced methylation of H3K4 in the nos2 promoter. Furthermore, cytokine-induced nos2 expression was reduced in isolated islets from set7/9 knockout mice compared to wild type mice. Our findings suggest that Set7/9 contributes to islet nos2 transcription through activating histone modifications.