| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
Set7/9 is an enzyme that methylates lysine 4 of histone 3 (H3K4) to maintain euchromatin. While Set7/9 contributes to the transactivation of beta cell specific genes, Set7/9 also reportedly binds NF-kB to regulate inflammatory 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 in islet inflammation. To induce inflammation, mouse beta insulinoma cells were treated with a cocktail of pro-inflammatory cytokines. Cytokine treatment induced the expression of iNOS and apoptosis, which were attenuated by Set7/9 knockdown. Set7/9 made complex with NF-kB and was recruited on NF-kB binding site of Nos2 gene to methylate H3K4 in response to cytokine treatment. 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 Nos2 transcription through histone modifications in beta cells.
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