Deciphering the Mechanical code of the genome and epigenome

Basu, Aakash; Bobrovnikov, Dmitriy G.; Cieza, Basilio; Arcon, Juan Pablo ; Orozco, Modesto; Ha, Taekjip

Abstract

Diverse DNA-deforming processes are impacted by the local mechanical and structural properties of DNA, which in turn depend on local sequence and epigenetic modifications. Deciphering this mechanical code (that is, this dependence) has been challenging due to the lack of high-throughput experimental methods. Here we present a comprehensive characterization of the mechanical code. Utilizing high-throughput measurements of DNA bendability via loop-seq, we quantitatively established how the occurrence and spatial distribution of dinucleotides, tetranucleotides and methylated CpG impact DNA bendability. We used our measurements to develop a physical model for the sequence and methylation dependence of DNA bendability. We validated the model by performing loop-seq on mouse genomic sequences around transcription start sites and CTCF-binding sites. We applied our model to test the predictions of all-atom molecular dynamics simulations and to demonstrate that sequence and epigenetic modifications can mechanically encode regulatory information in diverse contexts.

Citation

Basu, A., Bobrovnikov, D. G., Cieza, B., Arcon, J. P., Orozco, M., & Ha, T. (2022). Deciphering the Mechanical code of the genome and epigenome. Nature Structural and Molecular Biology, 29, 1178-1187. https://doi.org/10.1101/2020.08.22.262352

• Journal Article Type: Article
• Acceptance Date: Oct 18, 2022
• Online Publication Date: Dec 5, 2022
• Publication Date: Dec 5, 2022
• Deposit Date: Jul 12, 2022
• Publicly Available Date: Jun 6, 2023
• Journal: Nature Structural and Molecular Biology
• Print ISSN: 1545-9993
• Electronic ISSN: 1545-9985
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 29
• Pages: 1178-1187
• DOI: https://doi.org/10.1101/2020.08.22.262352
• Public URL: https://durham-repository.worktribe.com/output/1200553