期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 25, 页码 14322-14330出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2002933117
关键词
epigenetics; DNA modification; ChIP-seq; DNA target selection; restriction-modification
资金
- National Natural Science Foundation of China [31720103906, 31925002]
- China National Key Research and Development Program [2019YFA0904300]
- Fundamental Research Funds for the Central Universities of China
- SMART Antimicrobial Resistance Interdisciplinary Research Group - National Research Foundation of Singapore
- US National Science Foundation [CHE-1709364]
- NIH [R35GM130376]
- China Scholarship Council [201606270163]
- University of Southern California-Taiwan Postdoctoral Fellowship
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.
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