Abstract

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.

Data availability

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).

The following previously published data sets were used

Article and author information

Author details

  1. Sung Hyun Kim

    Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9272-7036
  2. Mahipal Ganji

    Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Eugene Kim

    Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Jaco van der Torre

    Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Elio Abbondanzieri

    Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, Netherlands
    For correspondence
    elio.abbondanzieri@rochester.edu
    Competing interests
    The authors declare that no competing interests exist.
  6. Cees Dekker

    Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, Delft, Netherlands
    For correspondence
    C.Dekker@tudelft.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6273-071X

Funding

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.

Reviewing Editor

  1. Michael T Laub, Massachusetts Institute of Technology, United States

Version history

  1. Received: March 10, 2018
  2. Accepted: December 6, 2018
  3. Accepted Manuscript published: December 7, 2018 (version 1)
  4. Version of Record published: December 20, 2018 (version 2)

Copyright

© 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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  1. Sung Hyun Kim
  2. Mahipal Ganji
  3. Eugene Kim
  4. Jaco van der Torre
  5. Elio Abbondanzieri
  6. Cees Dekker
(2018)
DNA sequence encodes the position of DNA supercoils
eLife 7:e36557.
https://doi.org/10.7554/eLife.36557

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