Convergence of DNA methylation and phosphorothioation epigenetics in bacterial genomes

Chen Chao; Wang Lianrong; Chen SiWu XiaolinGu MeijiaChen XiJiang SusuWang YunfuDeng ZixinDedon Peter C.Chen Shi

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Convergence of DNA methylation and phosphorothioation epigenetics in bacterial genomes

机译：Convergence of DNA methylation and phosphorothioation epigenetics in bacterial genomes

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Explosive growth in the study of microbial epigenetics has revealed a diversity of chemical structures and biological functions of DNA modifications in restriction-modification (R-M) and basic genetic processes. Here, we describe the discovery of shared consensus sequences for two seemingly unrelated DNA modification systems, (6m)A methylation and phosphorothioation (PT), in which sulfur replaces a nonbridging oxygen in the DNA backbone. Mass spectrometric analysis of DNA from Escherichia coli B7A and Salmonella enterica serovar Cerro 87, strains possessing PT-based R-M genes, revealed d(G(PS)(6m)A) dinucleotides in the G(PS)(6m)AAC consensus representing similar to 5 of the 1,100 to 1,300 PT-modified d(G(PS)A) motifs per genome, with (6m)A arising from a yet-to-be-identified methyltransferase. To further explore PT and (6m)A in another consensus sequence, G(PS)(6m)ATC, we engineered a strain of E. coli HST04 to express Dnd genes from Hahella chejuensis KCTC2396 (PT in G(PS)ATC) and Dam methyltransferase from E. coli DH10B ((6m)A in G(6m)ATC). Based on this model, in vitro studies revealed reduced Dam activity in G(PS)ATC-containing oligonucleotides whereas single-molecule real-time sequencing of HST04 DNA revealed (6m)A in all 2,058 G(PS)ATC sites (5 of 37,698 total GATC sites). This model system also revealed temperature-sensitive restriction by DndFGH in KCTC2396 and B7A, which was exploited to discover that (6m)A can substitute for PT to confer resistance to restriction by the DndFGH system. These results point to complex but unappreciated interactions between DNA modification systems and raise the possibility of coevolution of interacting systems to facilitate the function of each.

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《Proceedings of the National Academy of Sciences of the United States of America.》 |2017年第17期|4501-4506|共6页
作者
Chen Chao; Wang Lianrong; Chen SiWu XiaolinGu MeijiaChen XiJiang SusuWang YunfuDeng ZixinDedon Peter C.Chen Shi;
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作者单位

Wuhan Univ, Sch Pharmaceut Sci, Minist Educ, Key Lab Combinatorial Biosynth & Drug Discov, Wuhan 430071, Peoples R China;

MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA;

Hubei Univ Med, Taihe Hosp, Shiyan 442000, Hubei, Peoples R China;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
DNA phosphorothioation; DNA methylation; epigenetics; restriction-modification; bioanalytical chemistry;

Convergence of DNA methylation and phosphorothioation epigenetics in bacterial genomes

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