Summary
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, using a high-throughput single-molecule technique, we visualize plectonemes, the extended intertwined DNA loops that form upon twisting DNA. We discover that the underlying DNA sequence directly encodes the structure of supercoiled DNA by pinning plectonemes at specific positions. To explain this sequence-structure relationship, we develop a physical model that predicts the level of plectoneme pinning, in excellent agreement with the data. Intrinsic curvature is found to be the key property governing the supercoiled structure of DNA. By examining sequenced genomes, we show that plectonemes are likely to localize directly upstream of transcription start sites in Escherichia coli – a prediction that is experimentally verified in our measurements on such sequences. Our results reveal that DNA directly encodes for sequences that help to spatially organize the genome.