DNA sequence encodes the position of DNA supercoils
The three-dimensional organization of DNA is increasingly understood to play a decisive role in vital cellular processes. Many studies focus on the role of DNA-packaging proteins, crowding, and confinement in arranging chromatin, but structural information might also be directly encoded in bare DNA itself. Here we visualize plectonemes (extended intertwined DNA structures formed upon supercoiling) on individual DNA molecules. Remarkably, our experiments show that the DNA sequence directly encodes the structure of supercoiled DNA by pinning plectonemes at specific sequences. We develop a physical model that predicts that sequence-dependent intrinsic curvature is the key determinant of pinning strength and demonstrate this simple model provides very good agreement with the data. Analysis of several prokaryotic genomes indicates that plectonemes localize directly upstream of promoters, which we experimentaly confirm for selected promotor sequences. Our findings reveal a hidden code in the genome that helps to spatially organize the chromosomal DNA.
All data generated or analysed during this study are included in the manuscript and supporting files. The previously published genome data for E. coli used in Figure 4B can be accessed here http://regulondb.ccg.unam.mx/menu/download/datasets/files/PromoterSet.txt; V. cholerae here http://www.pnas.org/highwire/filestream/618514/field_highwire_adjunct_files/2/pnas.1500203112.sd02.xlsx; B. methanolicus here https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342826/bin/12864_2015_1239_MOESM2_ESM.xlsx; M. tuberculosis here https://ars.els-cdn.com/content/image/1-s2.0-S2211124713006153-mmc2.xlsx; and C. crescentus here https://doi.org/10.1371/journal.pgen.1004831.s012. The previously published genome data for D. melanogaster, C. elegans, A. thaliana, S. cerevisiae, and S. pombe used in Figure 4E can be accessed using the Eukaryotic Promotor Database (https://epd.vital-it.ch).
Whole genome sequence data: E. ColiNCBI Genome, NC_000913.3.
Whole genome sequence data: S. cerevisiase (Chr I)NCBI Nucleotide, NC_001133.9.
Whole genome sequence data: S. cerevisiase (Chr II)NCBI Nucleotide, NC_001134.8.
Whole genome sequence data: S. cerevisiase (Chr III)NCBI Nucleotide, NC_001135.5.
Whole genome sequence data: S. cerevisiase (Chr IV)NCBI Nucleotide, NC_001136.10.
Whole genome sequence data: S. cerevisiase (Chr V)NCBI Nucleotide, NC_001137.3.
Whole genome sequence data: S. cerevisiase (Chr VI)NCBI Nucleotide, NC_001138.5.
Whole genome sequence data: S. cerevisiase (Chr VII)NCBI Nucleotide, NC_001139.9.
Whole genome sequence data: S. cerevisiase (Chr VIII)NCBI Nucleotide, NC_001140.6.
Whole genome sequence data: S. cerevisiase (Chr IX)NCBI Nucleotide, NC_001141.2.
Whole genome sequence data: S. cerevisiase (Chr X)NCBI Nucleotide, NC_001142.9.
Whole genome sequence data: S. cerevisiase (Chr XI)NCBI Nucleotide, NC_001143.9.
Whole genome sequence data: S. cerevisiase (Chr XII)NCBI Nucleotide, NC_001144.5.
Whole genome sequence data: S. cerevisiase (Chr XIII)NCBI Nucleotide, NC_001145.3.
Whole genome sequence data: S. cerevisiase (Chr XIV)NCBI Nucleotide, NC_001146.8.
Whole genome sequence data: S. cerevisiase (Chr XV)NCBI Nucleotide, NC_001147.6.
Whole genome sequence data: S. cerevisiase (Chr XVI)NCBI Nucleotide, NC_001148.4.
Whole genome sequence data: S. cerevisiaseNCBI Nucleotide, NC_001224.1.
Article and author information
H2020 European Research Council (669598)
- Cees Dekker
The Netherlands Organization for Scientific Research (the Frontiers of Nanoscience program)
- Elio Abbondanzieri
H2020 European Research Council (304284)
- Elio Abbondanzieri
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Michael T Laub, Massachusetts Institute of Technology, United States
- Received: March 10, 2018
- Accepted: December 6, 2018
- Accepted Manuscript published: December 7, 2018 (version 1)
- Version of Record published: December 20, 2018 (version 2)
© 2018, Kim et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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