Supramolecular Coordination-Directed Reversible Regulation of Protein Activities at Epigenetic DNA Marks

doi:10.1021/jacs.8b09113

	Supramolecular Coordination-Directed Reversible Regulation of Protein Activities at Epigenetic DNA Marks
	Xiong, Wei 1; Wang, Shao-Ru 1; Wang, Jia-Qi 1; Fu, Bo-Shi 2; Chen, Kun 1; Wei, Lai 1; Qing, Guangyan 3; Tian, Tian 1; Zhou, Xiang 1
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.