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Metabolic regulation of gene expression by histone lactylation
文献类型：期刊论文
| 作者 | Zhang, Di2; Tang, Zhanyun3; Huang, He2,11; Zhou, Guolin2; Cui, Chang2; Weng, Yejing2; Liu, Wenchao2; Kim, Sunjoo4; Lee, Sangkyu4; Perez-Neut, Mathew2 |
| 刊名 | NATURE
 |
| 出版日期 | 2019-10-24 |
| 卷号 | 574期号:7779页码:575-+ |
| ISSN号 | 0028-0836 |
| DOI | 10.1038/s41586-019-1678-1 |
| 通讯作者 | Becker, Lev(levb@uchicago.edu) ; Zhao, Yingming(yingming.zhao@uchicago.edu) |
| 英文摘要 | The Warburg effect, which originally described increased production of lactate in cancer, is associated with diverse cellular processes such as angiogenesis, hypoxia, polarization of macrophages and activation of T cells. This phenomenon is intimately linked to several diseases including neoplasia, sepsis and autoimmune diseases(1,2). Lactate, which is converted from pyruvate in tumour cells, is widely known as an energy source and metabolic by-product. However, its non-metabolic functions in physiology and disease remain unknown. Here we show that lactate-derived lactylation of histone lysine residues serves as an epigenetic modification that directly stimulates gene transcription from chromatin. We identify 28 lactylation sites on core histones in human and mouse cells. Hypoxia and bacterial challenges induce the production of lactate by glycolysis, and this acts as a precursor that stimulates histone lactylation. Using M1 macrophages that have been exposed to bacteria as a model system, we show that histone lactylation has different temporal dynamics from acetylation. In the late phase of M1 macrophage polarization, increased histone lactylation induces homeostatic genes that are involved in wound healing, including Arg1. Collectively, our results suggest that an endogenous 'lactate clock' in bacterially challenged M1 macrophages turns on gene expression to promote homeostasis. Histone lactylation thus represents an opportunity to improve our understanding of the functions of lactate and its role in diverse pathophysiological conditions, including infection and cancer. |
| WOS关键词 | TRANSCRIPTIONAL ACTIVATION ; READ ALIGNMENT ; HALLMARKS ; CANCER ; P300 |
| 资助项目 | University of Chicago ; Nancy and Leonard Florsheim family fund ; NIH[R01GM115961] ; NIH[R01DK118266] ; NIH[R01DK102960] ; NIH[R01HL137998] ; NIH[R01CA129325] ; NIH[R01DK071900] ; NIH[NSF1808087] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| 出版者 | NATURE PUBLISHING GROUP |
| WOS记录号 | WOS:000492991700058 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/281897]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Becker, Lev; Zhao, Yingming |
| 作者单位 | 1.Sichuan Univ, West China Hosp, Dept Gen Practice, State Key Lab Biotherapy, Chengdu, Sichuan, Peoples R China 2.Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA 3.Rockefeller Univ, Lab Biochem & Mol Biol, 1230 York Ave, New York, NY 10021 USA 4.Kyungpook Natl Univ, Pharmaceut Sci Res Inst, Coll Pharm, BK21 Plus KNU Multiom Based Creat Drug Res Team, Daegu, South Korea 5.Univ Chicago, Dept Microbiol, Chicago, IL 60637 USA 6.Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA 7.Univ Calif San Diego, Sch Med, Ctr Epigen, La Jolla, CA 92093 USA 8.Univ Calif San Diego, Sch Med, Dept Cellular & Mol Med, La Jolla, CA 92093 USA 9.Univ Georgia, Dept Pharmaceut & Biomed Sci, Athens, GA 30602 USA 10.Univ Chicago Med, Ctr Comprehens Canc, Chicago, IL 60637 USA |
| 推荐引用方式 GB/T 7714 | Zhang, Di,Tang, Zhanyun,Huang, He,et al. Metabolic regulation of gene expression by histone lactylation[J]. NATURE,2019,574(7779):575-+. |
| APA | Zhang, Di.,Tang, Zhanyun.,Huang, He.,Zhou, Guolin.,Cui, Chang.,...&Zhao, Yingming.(2019).Metabolic regulation of gene expression by histone lactylation.NATURE,574(7779),575-+. |
| MLA | Zhang, Di,et al."Metabolic regulation of gene expression by histone lactylation".NATURE 574.7779(2019):575-+. |
入库方式： OAI收割
来源：上海药物研究所
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