PT  - JOURNAL ARTICLE
AU  - Sung Hyun Kim
AU  - Mahipal Ganji
AU  - Jaco van der Torre
AU  - Elio Abbondanzieri
AU  - Cees Dekker
TI  - DNA sequence encodes the position of DNA supercoils
AID  - 10.1101/180414
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 180414
4099  - http://biorxiv.org/content/early/2017/08/24/180414.short
4100  - http://biorxiv.org/content/early/2017/08/24/180414.full
AB  - The three-dimensional structure of DNA is increasingly understood to play a decisive role in gene regulation and other vital cellular processes1, which has triggered an explosive growth of research on the spatial architecture of the genome2,3. Much of this research focuses on the role of various proteins that act on DNA in organizing chromatin4–11, but structural information might also be directly encoded in bare DNA itself. Here, using a high-throughput single-molecule technique to visualize DNA plectonemes (extended intertwined DNA loops that form upon twisting DNA)12, we discover that DNA sequence directly governs the structure of supercoiled DNA. We observe that certain sequences do strongly pin plectonemes to a local position. To explain this sequence – structure relationship, we develop a physical model that accommodates the local intrinsic curvature and flexibility of DNA, which predicts the level of plectoneme pinning, in excellent agreement with the data. Intrinsic curvature is found to be the major factor governing the supercoiled structure of DNA. Analysis of the Escherichia coli genome predicts that plectonemes are likely to form directly upstream of transcription start sites – a prediction that is experimentally verified in our measurements on such sequences. Our results indicate that DNA encodes for sequences that help to spatially organize the genome.