The regulatory enzymes and protein substrates for the lysine beta-hydroxybutyrylation pathway
文献类型：期刊论文
| 作者 | Huang, He2,3; Zhang, Di4; Weng, Yejing4; Delaney, Kyle4; Tang, Zhanyun5; Yan, Cong2,3; Qi, Shankang2,3; Peng, Chao4,6; Cole, Philip A.1; Roeder, Robert G.5 |
| 刊名 | SCIENCE ADVANCES
 |
| 出版日期 | 2021-02-01 |
| 卷号 | 7期号:9页码:10 |
| ISSN号 | 2375-2548 |
| DOI | 10.1126/sciadv.abe2771 |
| 通讯作者 | Huang, He(hhuang@simm.ac.cn) ; Zhao, Yingming(yingming.zhao@uchicago.edu) |
| 英文摘要 | Metabolism-mediated epigenetic changes represent an adapted mechanism for cellular signaling, in which lysine acetylation and methylation have been the historical focus of interest. We recently discovered a beta-hydroxybutyrate-mediated epigenetic pathway that couples metabolism to gene expression. However, its regulatory enzymes and substrate proteins remain unknown, hindering its functional study. Here, we report that the acyltransferase p300 can catalyze the enzymatic addition of beta-hydroxybutyrate to lysine (Kbhb), while histone deacetylase 1 (HDAC1) and HDAC2 enzymatically remove Kbhb. We demonstrate that p300-dependent histone Kbhb can directly mediate in vitro transcription. Moreover, a comprehensive analysis of Kbhb substrates in mammalian cells has identified 3248 Kbhb sites on 1397 substrate proteins. The dependence of histone Kbhb on p300 argues that enzyme-catalyzed acylation is the major mechanism for nuclear Kbhb. Our study thus reveals key regulatory elements for the Kbhb pathway, laying a foundation for studying its roles in diverse cellular processes. |
| 资助项目 | University of Chicago ; Leonard Florsheim Family Fund ; NIH[DK071900] ; NIH[CA129325] ; NIH[GM135504] ; NIH[GM62437] ; NIH[DK118266] ; National Natural Science Foundation of China[81973164] ; Shanghai Pujiang Program[19PJ1411200] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000622481300026 |
| 出版者 | AMER ASSOC ADVANCEMENT SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/295877]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Huang, He; Zhao, Yingming |
| 作者单位 | 1.Harvard Med Sch, Brigham & Womens Hosp, Div Genet, Dept Biol Chem & Mol Pharmacol,Dept Med, Boston, MA 02115 USA 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA 5.Rockefeller Univ, Lab Biochem & Mol Biol, New York, NY 10065 USA 6.Chinese Acad Sci, Shanghai Adv Res Inst, Zhangjiang Lab, Natl Facil Prot Sci Shanghai, Shanghai 201210, Peoples R China |
| 推荐引用方式 GB/T 7714 | Huang, He,Zhang, Di,Weng, Yejing,et al. The regulatory enzymes and protein substrates for the lysine beta-hydroxybutyrylation pathway[J]. SCIENCE ADVANCES,2021,7(9):10. |
| APA | Huang, He.,Zhang, Di.,Weng, Yejing.,Delaney, Kyle.,Tang, Zhanyun.,...&Zhao, Yingming.(2021).The regulatory enzymes and protein substrates for the lysine beta-hydroxybutyrylation pathway.SCIENCE ADVANCES,7(9),10. |
| MLA | Huang, He,et al."The regulatory enzymes and protein substrates for the lysine beta-hydroxybutyrylation pathway".SCIENCE ADVANCES 7.9(2021):10. |
入库方式： OAI收割
来源：上海药物研究所
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