Measuring DNA mechanics on the genome scale

Aakash Basu, Dmitriy G. Bobrovnikov, Zan Qureshi, Tunc Kayikcioglu, Thuy T. M. Ngo, Anand Ranjan, Sebastian Eustermann, Basilio Cieza, Michael T. Morgan, Miroslav Hejna, H. Tomas Rube, Karl-Peter Hopfner, Cynthia Wolberger, Jun S. Song and Taekjip Ha ()
Additional contact information
Aakash Basu: Johns Hopkins University School of Medicine
Dmitriy G. Bobrovnikov: Johns Hopkins University School of Medicine
Zan Qureshi: Johns Hopkins University
Tunc Kayikcioglu: University of Illinois at Urbana-Champaign
Thuy T. M. Ngo: University of Illinois at Urbana-Champaign
Anand Ranjan: Johns Hopkins University
Sebastian Eustermann: Ludwig-Maximilians-Universität
Basilio Cieza: Johns Hopkins University
Michael T. Morgan: Johns Hopkins University School of Medicine
Miroslav Hejna: University of Illinois at Urbana-Champaign
H. Tomas Rube: University of Illinois at Urbana-Champaign
Karl-Peter Hopfner: Ludwig-Maximilians-Universität
Cynthia Wolberger: Johns Hopkins University School of Medicine
Jun S. Song: University of Illinois at Urbana-Champaign
Taekjip Ha: Johns Hopkins University School of Medicine

Nature, 2021, vol. 589, issue 7842, 462-467

Abstract: Abstract Mechanical deformations of DNA such as bending are ubiquitous and have been implicated in diverse cellular functions1. However, the lack of high-throughput tools to measure the mechanical properties of DNA has limited our understanding of how DNA mechanics influence chromatin transactions across the genome. Here we develop ‘loop-seq’—a high-throughput assay to measure the propensity for DNA looping—and determine the intrinsic cyclizabilities of 270,806 50-base-pair DNA fragments that span Saccharomyces cerevisiae chromosome V, other genomic regions, and random sequences. We found sequence-encoded regions of unusually low bendability within nucleosome-depleted regions upstream of transcription start sites (TSSs). Low bendability of linker DNA inhibits nucleosome sliding into the linker by the chromatin remodeller INO80, which explains how INO80 can define nucleosome-depleted regions in the absence of other factors2. Chromosome-wide, nucleosomes were characterized by high DNA bendability near dyads and low bendability near linkers. This contrast increases for deeper gene-body nucleosomes but disappears after random substitution of synonymous codons, which suggests that the evolution of codon choice has been influenced by DNA mechanics around gene-body nucleosomes. Furthermore, we show that local DNA mechanics affect transcription through TSS-proximal nucleosomes. Overall, this genome-scale map of DNA mechanics indicates a ‘mechanical code’ with broad functional implications.

Date: 2021
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DOI: 10.1038/s41586-020-03052-3

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