TY - JOUR
T1 - Measuring DNA mechanics on the genome scale
AU - Basu, Aakash
AU - Bobrovnikov, Dmitriy G.
AU - Qureshi, Zan
AU - Kayikcioglu, Tunc
AU - Ngo, Thuy T.M.
AU - Ranjan, Anand
AU - Eustermann, Sebastian
AU - Cieza, Basilio
AU - Morgan, Michael T.
AU - Hejna, Miroslav
AU - Rube, H. Tomas
AU - Hopfner, Karl Peter
AU - Wolberger, Cynthia
AU - Song, Jun S.
AU - Ha, Taekjip
N1 - Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/1/21
Y1 - 2021/1/21
N2 - 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.
AB - 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.
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U2 - 10.1038/s41586-020-03052-3
DO - 10.1038/s41586-020-03052-3
M3 - Article
C2 - 33328628
AN - SCOPUS:85097598186
SN - 0028-0836
VL - 589
SP - 462
EP - 467
JO - Nature
JF - Nature
IS - 7842
ER -