DNA sequence encodes the position of DNA supercoils

Abstract

The three-dimensional structure of DNA is increasingly understood to play a decisive role in gene regulation and other vital cellular processes, which has triggered an explosive growth of research on the spatial architecture of the genome. Many studies focus on the role of various DNA-packaging proteins, crowding, and confinement in organizing chromatin, but structural information might also be directly encoded in bare DNA itself. Here, we use a fluorescence-based single-molecule technique to visualize plectonemes, the extended intertwined DNA loops that form upon twisting DNA. Remarkably, we find that the underlying DNA sequence directly encodes the structure of supercoiled DNA by pinning plectonemes at specific positions. We explore a variety of DNA sequences to determine what features influence pinning, and we develop a physical model that predicts the level of plectoneme pinning in excellent agreement with the data. The intrinsic curvature measured over a range of ~70 base pairs is found to be the key property governing the supercoiled structure of DNA. Our model predicts that plectonemes are likely to localize directly upstream of prokaryotic transcription start sites, and this prediction is experimentally verified in vitro. Our results reveal a hidden code in DNA that helps to spatially organize the genome.