2015 Fiscal Year Final Research Report
Molecular basis of metabolic reprogramming by chromatin conversion
| Project Area | Crosstalk of transcriptional control and energy pathways by hub metabolites |
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| Project/Area Number |
23116009
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2011-04-01 – 2016-03-31
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| Keywords | 代謝調節 / クロマチン / 遺伝子発現 / リジン脱メチル化 / フラビン / 脂肪細胞 / 癌細胞 |
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| Outline of Final Research Achievements |
Epigenetic marks such as methylation of DNA and histones are stably maintained or dynamically changed for gene regulation. The epigenetic states may be reprogrammed by environmental stimuli and inherited as the cellular memory. In fact, epigenetic alteration of disease-related genes is implicated in metabolic diseases and cancer. This study showed that the lysine demethylase LSD1, a nuclear enzyme which utilizes the flavin adenosine dinucleotide (FAD) as a cofactor, regulates energy metabolism in mouse adipocytes. Our data suggest that FAD-dependent demethylation by LSD1 suppresses energy expenditure genes under obese condition. Further, we found that overexpressed LSD1 changes the balance of oxidative phosphorylation and glycolysis in cancer cells, and that LSD2, another family member, works for protecting lipotoxicity in hepatic cells. These indicate that the LSD1 family proteins have an essential role in metabolic reprogramming in various cell types.
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| Free Research Field |
分子遺伝学
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