Recently, the prestigious international journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) published the research findings on phosphorothioate DNA modification in bacteria by Prof. Wang Lianrong’s team (School of Pharmaceutical Sciences, Wuhan University). The research reveals the target site selectivity of phosphorothioate DNA modification and its relationships with the three-dimensional structure of DNA and DNA methylation, and also illustrates the interaction between two completely different types of DNA modification in the same bacteria.
The paper is entitled Epigenetic competition reveals density-dependent regulation and target site plasticity of phosphorothioate epigenetics in bacteria. The two co-first authors are doctoral candidate Wu Xiaolin (School of Pharmaceutical Sciences, WHU) and Prof. Cao Bo (Qufu Normal University). Wuhan University is the first undersigned unit of the paper, and the corresponding authors are Prof. Wang Lianrong from Wuhan University, James E. Galagan from Boston University and Peter C. Dedon from the Massachusetts Institute of Technology.
Phosphorothioate DNA modification is a sulfur-containing modification in the phosphate backbone of DNA, and its target site sequence varies in different bacteria. Based on the experiments of Salmonella enterica containing both GAAC/GTTC phosphorothioate modification and GATC methylation modification, the study revealed a novel epigenetic regulatory mechanism of phosphorothioate DNA modification. While structurally similar GAAC, GTTC and GATC motifs can be identified by DNA phosphorylation modified proteins, the methylation of GATC can block PT modification of GATC and shift the PT modification site to GAAC/GTTC.
As a result, with methylation modification, the main modification sites in Salmonella enterica are GAAC/GTTC motifs. With the removal of the methylation gene, phosphorothioate modifications in the genome are half shifted to the GATC sequence, while their overall numbers in the bacteria remain stable.
Composed of four ATCG bases which constitute the genetic materials encoding the life signal, DNA has various epigenetic modifications to regulate life activities without changing the genetic code. Usually a bacterium contains more than one DNA modification system to perform or restrict epigenetic modification functions. The research team discovered the interaction between two completely different types of DNA modification in the same bacteria, and proved the relationships between the target site specificity of phosphorothioate DNA modification and DNA structure as well as DNA methylation, allowing us to fully deepen our understanding of the interplay of different epigenetic modification systems. The research comprehensively embodies many key achievements including protein-DNA interaction, DNA modification omics, and computer simulation, so that it expands the new research field concerning the interaction between PT modification and other DNA epigenetic modifications.
Phosphorothioate DNA modification sites in the genome would change with the presence or absence of Dam methylation. When there is a Dam methylation (red ball), the main PT modification (gold ball) sites in the genome lie at GAAC/GTTC (outer circle: orange and yellow). After the Dam methyltransferase gene is knocked out, the main PT modification sites transfer to GATC sites (inner circle: green).
It is reported that Prof. Wang Lianrong, as the only or co-corresponding author, and his research group have headed the research of DNA phosphorylation in bacteria and its related fields. Their findings have been successively published in prestigious publications such as Nature Microbiology, PNAS, Nature Communications, mBio, Medicinal Research Reviews and Analytical Chemistry.
Paper link: https://www.pnas.org/content/117/25/14322
Website of Wang Lianrong’s Research Group: http://www.lianronglab.com
Written by: Yao Yuan
Rewritten by: Lin Wanping
Edited by: Zhu Tong
