DOT1L Regulates Thermogenic Adipocyte Differentiation and Function via Modulating H3K79 Methylation
文献类型：期刊论文
| 作者 | Shuai, Lin1; Li, Bo-Han1,2; Jiang, Hao-Wen1; Yang, Lin1,2; Li, Jia1,2,3 ; Li, Jing-Ya1,2,3
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| 刊名 | DIABETES
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| 出版日期 | 2021-06-01 |
| 卷号 | 70期号:6页码:1317-1333 |
| ISSN号 | 0012-1797 |
| DOI | 10.2337/db20-1110 |
| 通讯作者 | Li, Jia(jli@simm.ac.cn) ; Li, Jing-Ya(jyli@simm.ac.cn) |
| 英文摘要 | Brown and beige adipocytes are characterized as thermogenic adipocytes and have great potential for treating obesity and associated metabolic diseases. In this article, we identify a conserved mammalian lysine 79 of histone H3 (H3K79) methyltransferase, disruptor of telomeric silencing-1 like (DOT1L), as a new epigenetic regulator that controls thermogenic adipocyte differentiation and function. We show that deletion of DOT1L in thermogenic adipocytes potently protects mice from diet-induced obesity, improves glucose homeostasis, alleviates hepatic steatosis, and facilitates adaptive thermogenesis in vivo. Loss of DOT1L in primary preadipocytes significantly promotes brown and beige adipogenesis and thermogenesis in vitro. Mechanistically, DOT1L epigenetically regulates the brown adipose tissue-selective gene program by modulating H3K79 methylation, in particular H3K79me2 modification. Thus, our study demonstrates that DOT1L exerts an important role in energy homeostasis by regulating thermogenic adipocyte differentiation and function. |
| WOS关键词 | BROWN ADIPOSE-TISSUE ; GENE-EXPRESSION ; FAT DEVELOPMENT ; LEPTIN LEVELS ; CELL FATE ; BEIGE ; PRDM16 ; PGC-1-ALPHA ; REPRESSION ; MUSCLE |
| 资助项目 | China Postdoctoral Science Foundation[2018M642118] ; National Natural Science Foundation of China[81673493] ; National Program on Key Research Project[2016YFC1305505] ; National Science and Technology Major Project of China[2018ZX09711002-018] ; K.C. Wong Education Foundation |
| WOS研究方向 | Endocrinology & Metabolism |
| 语种 | 英语 |
| 出版者 | AMER DIABETES ASSOC |
| WOS记录号 | WOS:000671940300012 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/296972]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Li, Jia; Li, Jing-Ya |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Beijing, Peoples R China 3.Univ Chinese Acad Sci, Sch Pharmaceut Sci & Technol, Hangzhou Inst Adv Study, Hangzhou, Peoples R China |
| 推荐引用方式 GB/T 7714 | Shuai, Lin,Li, Bo-Han,Jiang, Hao-Wen,et al. DOT1L Regulates Thermogenic Adipocyte Differentiation and Function via Modulating H3K79 Methylation[J]. DIABETES,2021,70(6):1317-1333. |
| APA | Shuai, Lin,Li, Bo-Han,Jiang, Hao-Wen,Yang, Lin,Li, Jia,&Li, Jing-Ya.(2021).DOT1L Regulates Thermogenic Adipocyte Differentiation and Function via Modulating H3K79 Methylation.DIABETES,70(6),1317-1333. |
| MLA | Shuai, Lin,et al."DOT1L Regulates Thermogenic Adipocyte Differentiation and Function via Modulating H3K79 Methylation".DIABETES 70.6(2021):1317-1333. |
入库方式： OAI收割
来源：上海药物研究所
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