Mechanisms of brown fat differentiation through chromatin modification
| Project/Area Number |
16H06226
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
Ohno Haruya 広島大学, 医歯薬保健学研究科(医), 助教 (60725894)
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| Research Collaborator |
Nagano Gaku
Morita Yoshimi
Egusa Gentaro
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥20,540,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥4,740,000)
Fiscal Year 2018: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2017: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2016: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
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| Keywords | 褐色脂肪細胞 / ベージュ脂肪細胞 / 糖尿病 / 発生・分化 / ヒストン修飾 / 細胞・組織 |
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| Outline of Final Research Achievements |
The purpose of this study is to explore and analyze a new epigenetic factor that can modulate differentiation and function of brown adipocytes and beige adipocytes. We identified methionine adenosyltransferase II α(MATIIα), a synthetase of methyl donor S-adenosylmethionine, as a newly binding partner of a PRDM16/EHMT1 transcriptional complex. Genetic ablation of MATIIαcauses a loss of brown adipose tissue in vivo. Depletion of MATIIα in brown adipocytes or beige adipocytes induced demethylation of H3K9 at a promoter region of white adipocyte specific genes and caused reductions of thermogenic genes such as ucp1. These findings revealed a novel mechanism that MATIIα modulate differentiation of brown adipocytes through chromatin modification.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究によりMATIIαがエピジェネティック調節機構を介して褐色脂肪細胞およびベージュ脂肪細胞の分化調節を行っているだけでなく、クレアチン生合成を介したUCP1非依存的な熱産性能をも制御しているという多面的な機能が明らかとなった．褐色脂肪細胞やベージュ脂肪細胞はエネルギーを熱として散逸させることができ，肥満症や糖尿病治療への応用が期待されている．今後MATIIαを含む転写複合体の機能解析を通じて褐色脂肪細胞やベージュ脂肪細胞の分化を促進させることや，UCP1に依存しない熱産生能を活性化させることができれば，糖尿病や肥満症治療の新たな選択肢を提示することができると期待される．
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-activator PRDM16.2019
Author(s)
Nakatsu Y, Matsunaga Y, Yamamotoya T, Ueda K, Inoue MK, Mizuno Y, Nakanishi M, Sano T, Yamawaki Y, Kushiyama A, Sakoda H, Fujishiro M, Ryo A, Ono H, Minamino T, Takahashi SI, Ohno H, Yoneda M, Takahashi K, Ishihara H, Katagiri H, Nishimura F, Kanematsu T, Yamada T, Asano T.
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Journal Title
Cell Rep.
Volume: 26
Issue: 12
Pages: 3221-3230
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program.2017
Author(s)
Hiraike Y, Waki H, Yu J, Nakamura M, Miyake K, Nagano G, Nakaki R, Suzuki K, Kobayashi H, Yamamoto S, Sun W, Aoyama T, Hirota Y, Ohno H, Oki K, Yoneda M, White AP, Tseng YH, Cypess AM, Larsen TJ, Jespersen NZ, Scheele C, Tsutsumi S, Aburatani H, Yamauchi T, Kadowaki T
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Journal Title
Nature cell biology
Volume: 19(9)
Issue: 9
Pages: 1081-1092
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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