DNA sequence encodes the position of DNA supercoils
Sung Hyun Kim (TU Delft - BN/Cees Dekker Lab, Kavli institute of nanoscience Delft)
Mahipal Ganji (Ludwig Maximilians University, TU Delft - BN/Cees Dekker Lab, Kavli institute of nanoscience Delft, Max Planck Institute of Biochemistry)
Eugene Kim (Kavli institute of nanoscience Delft, TU Delft - BN/Cees Dekker Lab)
Jaco van der Torre (TU Delft - BN/Technici en Analisten, Kavli institute of nanoscience Delft)
Elio Abbondanzieri (TU Delft - BN/Bionanoscience, University of Rochester, Kavli institute of nanoscience Delft)
Cees Dekker (TU Delft - BN/Cees Dekker Lab, Kavli institute of nanoscience Delft)
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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 experimentally confirm for selected promotor sequences. Our findings reveal a hidden code in the genome that helps to spatially organize the chromosomal DNA.
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