| Project/Area Number |
15H04851
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Metabolomics
|
|---|
| Research Institution | National Center for Global Health and Medicine |
|---|
Principal Investigator |
MATSUMOTO MICHIHIRO 国立研究開発法人国立国際医療研究センター, 研究所 糖尿病研究センター 分子代謝制御研究部, 部長 (90467663)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
KIDO Yoshiaki 神戸大学, 大学院・保健学研究科, 教授 (10335440)
INOUE Hiroshi 金沢大学, 新学術創成研究機構, 教授 (50397832)
|
|---|
| Research Collaborator |
SAKAI Mashito
MITSUSHIMA Masaru
NAGANUMA Takao
YANO Hiroyuki
YAGI Takashi
MATSUKAWA Toshiya
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2015: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
|
|---|
| Keywords | 代謝調節 / 転写 / 酵素 / エピゲノム修飾 / 肥満 / 糖尿病 / 肝臓 / 脂肪組織 / 遺伝子転写 / エピジェネティクス / 遺伝子 / 発現制御 / 代謝 |
|---|
| Outline of Final Research Achievements |
The role of KAT2A in hepatocytes was investigated in the regulation of fasting metabolism using loss-of-function approaches in vivo and in vitro. In the fasted state, hepatic KAT2A formed a signalling module with transcriptional coregulator CITED2 and PKA promoted transcription of fasting response genes, and thereby adapted to fasting. Mechanistically, KAT2A was phosphorylated by PKA within the module, switched its substrate from transcriptional coactivator PGC-1α to histone H3, and thereby promoted activation of this coactivator and epigenomic changes in the promoter, resulting in activation of such gene transcription. These results suggest that KAT2A is a cAMP-responsible acetyltransferase that is critical to integrate fasting metabolic response in hepatocytes.
|
