Ascorbic Acid Reprograms Epigenome and Epitranscriptome by Reducing Fe(III) in the Catalytic Cycle of Dioxygenases
文献类型：期刊论文
| 作者 | He, Weizhi1; Yin, Xiaotong1; Xu, Chu1; Liu, Xiangyue1; Huang, Yue2; Yang, Caiguang2 ; Xu, Yanhui1; Hu, Lulu1
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| 刊名 | ACS CHEMICAL BIOLOGY
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| 出版日期 | 2023-12-15 |
| 卷号 | 19期号:1页码:129-140 |
| ISSN号 | 1554-8929 |
| DOI | 10.1021/acschembio.3c00567 |
| 通讯作者 | Hu, Lulu(Luluhu@fudan.edu.cn) |
| 英文摘要 | Ascorbic acid (ASC) has been reported to stimulate DNA iterative oxidase ten-eleven translocation (TET) enzymes, Jumonji C-domain-containing histone demethylases, and potentially RNA m(6)A demethylases FTO and ALKBH5 as a cofactor. Although ascorbic acid has been widely investigated in reprogramming DNA and histone methylation status in vitro, in cultured cells and mouse models, its specific role in the catalytic cycle of dioxygenases remains enigmatic. Here, we systematically investigated the stimulation of ASC toward TET2, ALKBH3, histone demethylases, and FTO. We find that ASC reprograms epitranscriptome by erasing the hypermethylated m(6)A sites in mRNA. Biochemistry and electron spin resonance assays demonstrate that ASC enters the active pocket of dioxygenases and reduces Fe(III), either incorporated upon protein synthesis or generated upon rebounding the hydroxyl radical during oxidation, into Fe(II). Finally, we propose a remedied model for the catalytic cycle of dioxygenases by adding in the essential cofactor, ASC, which refreshes and regenerates inactive dioxygenase through recycling Fe(III) into Fe(II) in a dynamic "hit-and-run" manner. |
| WOS关键词 | VITAMIN-C ; DNA DEMETHYLATION ; 5-METHYLCYTOSINE ; RNA ; 5-HYDROXYMETHYLCYTOSINE ; 5-FORMYLCYTOSINE ; SUBSTRATE ; PROMOTES ; INSIGHT |
| 资助项目 | Natural Science Foundation of Shanghai Municipality[22142202400] ; Professional Technical Service Platform for Critical Diseases in Shanghai, China[2021YFA1100400] ; National Key R&D Program of China[92153303] ; National Natural Science Foundation of China[21ZR1480300] ; Natural science foundation of Shanghai Science and Technology Commission |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| 出版者 | AMER CHEMICAL SOC |
| WOS记录号 | WOS:001146455400001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/308772]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Hu, Lulu |
| 作者单位 | 1.Fudan Univ, Shanghai Med Coll, Canc Inst, Inst Biomed Sci,Shanghai Canc Ctr,Shanghai Key Lab, Shanghai 200032, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | He, Weizhi,Yin, Xiaotong,Xu, Chu,et al. Ascorbic Acid Reprograms Epigenome and Epitranscriptome by Reducing Fe(III) in the Catalytic Cycle of Dioxygenases[J]. ACS CHEMICAL BIOLOGY,2023,19(1):129-140. |
| APA | He, Weizhi.,Yin, Xiaotong.,Xu, Chu.,Liu, Xiangyue.,Huang, Yue.,...&Hu, Lulu.(2023).Ascorbic Acid Reprograms Epigenome and Epitranscriptome by Reducing Fe(III) in the Catalytic Cycle of Dioxygenases.ACS CHEMICAL BIOLOGY,19(1),129-140. |
| MLA | He, Weizhi,et al."Ascorbic Acid Reprograms Epigenome and Epitranscriptome by Reducing Fe(III) in the Catalytic Cycle of Dioxygenases".ACS CHEMICAL BIOLOGY 19.1(2023):129-140. |
入库方式： OAI收割
来源：上海药物研究所
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