Epigenetic competition reveals density-dependent regulation and target site plasticity of phosphorothioate epigenetics in bacteria
Name
14322.full.pdf
Description
Published version
Size
1.38 MB
Format
Unknown
Checksum (MD5)
9b68fddc9a4a4b0796c07c617596bbfa
Author(s)
Wu, Xiaolin
Cao, Bo
Aquino, Patricia
Chiu, Tsu-Pei
Chen, Chao
Jiang, Susu
Deng, Zixin
Chen, Shi
Rohs, Remo
Wang, Lianrong
Date Issued
2020
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
Proceedings of the National Academy of Sciences
Version
Final published version
Abstract
© 2020 National Academy of Sciences. All rights reserved. Phosphorothioate (PT) DNA modifications-in which a nonbonding phosphate oxygen is replaced with sulfur-represent a widespread, horizontally transferred epigenetic system in prokaryotes and have a highly unusual property of occupying only a small fraction of available consensus sequences in a genome. Using Salmonella enterica as a model, we asked a question of fundamental importance: How do the PT-modifying DndA-E proteins select their GPSAAC/GPSTTC targets? Here, we applied innovative analytical, sequencing, and computational tools to discover a novel behavior for DNA-binding proteins: The Dnd proteins are "parked" at the G6mATC Dam methyltransferase consensus sequence instead of the expected GAAC/GTTC motif, with removal of the 6mA permitting extensive PT modification of GATC sites. This shift in modification sites further revealed a surprising constancy in the density of PT modifications across the genome. Computational analysis showed that GAAC, GTTC, and GATC share common features of DNA shape, which suggests that PT epigenetics are regulated in a densitydependent manner partly by DNA shape-driven target selection in the genome.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Center for Environmental Health Sciences
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1073/PNAS.2002933117
