2016 Fiscal Year Final Research Report
The role of methyltransferase Set7/9 in pancreatic beta cells
| Project/Area Number |
26461345
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | メチル化 / Set7/9 / β細胞 / NF-kb / 炎症 / iNOS |
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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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| Free Research Field |
糖尿病
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