Supramolecular Coordination-Directed Reversible Regulation of Protein Activities at Epigenetic DNA Marks | |
Xiong, Wei1; Wang, Shao-Ru1; Wang, Jia-Qi1; Fu, Bo-Shi2; Chen, Kun1; Wei, Lai1; Qing, Guangyan3; Tian, Tian1; Zhou, Xiang1 | |
刊名 | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY |
2018-11-21 | |
卷号 | 140期号:46页码:15842-15849 |
ISSN号 | 0002-7863 |
DOI | 10.1021/jacs.8b09113 |
通讯作者 | Tian, Tian(ttian@whu.edu.cn) ; Zhou, Xiang(xzhou@whu.edu.cn) |
英文摘要 | In mammals, 5-formylcytosine (5fC) has been identified as an important mark, which plays significant roles in active DNA demethylation and also in epigenetic regulation. It is therefore important to target this epigenetic mark as well as manipulating DNA protein interactions at this site. A unique feature of 5fC is the presence of a formyl group at the C-5 position. In the current study, we introduce supramolecular coordination chemistry for reversible regulation of DNA-protein interactions on this mark. We have designed and synthesized the 2-(aminooxy)-N-(quinolin-8-yl)acetamide (AQA), which functions well in selective labeling of 5fC mark. Using this feature, the association and disassociation of metal ion supplementation allow blocking and deblocking of DNA-protein interactions. In addition, we synthesized a close analogue of AQA by replacing the nitrogen atom in the quinoline ring with a CH group. Importantly, the regulatory effects of those metal ion supplementations were completely erased. On the basis of the combined information, we propose a conformational flexibility in a side arm in response to switched coordination. In the absence of coordinating interaction, the flexible side arm probably takes on an extended conformation and points away from the hydrogen bonding cavity. Importantly, coordinating interaction is effective in imposing a restrained geometry to this side arm, with the quinoline ring being oriented opposite the complementary nucleobase. Moreover, the coordination-induced activity control can be reversed by supplementation with a number of chelating agents. The concept described is unique in installing an auxiliary side arm with bending flexibility to control oligonucleotide functions. Finally, these findings show promising potential of supramolecular coordination chemistry for DNA epigenetics. |
资助项目 | National Science Foundation of China[21722803] ; National Science Foundation of China[21721005] ; National Science Foundation of China[21572169] ; National Science Foundation of China[21877086] ; National Science Foundation of China[21672165] |
WOS关键词 | STATE KINETIC-ANALYSIS ; THYMINE DNA ; RESTRICTION ENZYME ; STEADY-STATE ; 5-FORMYLCYTOSINE ; POLYMERASE ; BASE ; 5-HYDROXYMETHYLCYTOSINE ; 5-CARBOXYLCYTOSINE ; TRANSCRIPTION |
WOS研究方向 | Chemistry |
语种 | 英语 |
出版者 | AMER CHEMICAL SOC |
WOS记录号 | WOS:000451496800042 |
资助机构 | National Science Foundation of China ; National Science Foundation of China ; National Science Foundation of China ; National Science Foundation of China ; National Science Foundation of China ; National Science Foundation of China ; National Science Foundation of China ; National Science Foundation of China |
内容类型 | 期刊论文 |
源URL | [http://cas-ir.dicp.ac.cn/handle/321008/166518] |
专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
通讯作者 | Tian, Tian; Zhou, Xiang |
作者单位 | 1.Wuhan Univ, Key Lab Biomed Polymers, Minist Educ, Coll Chem & Mol Sci, Wuhan 430072, Hubei, Peoples R China 2.China Med Univ, Dept Pharmacol, Sch Pharm, Shenyang 110122, Liaoning, Peoples R China 3.Chinese Acad Sci, Key Lab Separat Sci Analyt Chem, Dalian Inst Chem Phys, Dalian 116023, Liaoning, Peoples R China |
推荐引用方式 GB/T 7714 | Xiong, Wei,Wang, Shao-Ru,Wang, Jia-Qi,et al. Supramolecular Coordination-Directed Reversible Regulation of Protein Activities at Epigenetic DNA Marks[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2018,140(46):15842-15849. |
APA | Xiong, Wei.,Wang, Shao-Ru.,Wang, Jia-Qi.,Fu, Bo-Shi.,Chen, Kun.,...&Zhou, Xiang.(2018).Supramolecular Coordination-Directed Reversible Regulation of Protein Activities at Epigenetic DNA Marks.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,140(46),15842-15849. |
MLA | Xiong, Wei,et al."Supramolecular Coordination-Directed Reversible Regulation of Protein Activities at Epigenetic DNA Marks".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 140.46(2018):15842-15849. |
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