DNA's mechanical and structural properties, dictated by local sequence and epigenetic modifications, have significant influence over a variety of DNA-deforming processes. However, comprehending this 'mechanical code' has been a complex task due to the lack of high-throughput experimental methods. Dr. Basu's research endeavors to unlock this intricate code.

In this episode, we delve into Dr. Basu's groundbreaking research. Utilizing high-throughput measurements of DNA bendability through loop-seq, a technology developed by his team, Dr. Basu reveals how the occurrence and spatial distribution of dinucleotides, tetranucleotides, and methylated CpG influence DNA bendability.

Building on these findings, Dr. Basu's team developed a physical model that captures the sequence and methylation dependence of DNA bendability. The model was further validated by using loop-seq on mouse genomic sequences around transcription start sites and CTCF-binding sites.

The conversation also explores how the model was applied to test the predictions of all-atom molecular dynamics simulations and show that sequence and epigenetic modifications can mechanically encode regulatory information in various contexts.

Join us as we traverse the fascinating terrain of DNA's mechanical code with Dr. Basu, opening up new avenues in our understanding of genetics and molecular biology.

Key Words: DNA Bendability, Mechanical Code, Loop-seq, Dinucleotides, Tetranucleotides, Methylated CpG, All-atom Molecular Dynamics Simulations, Epigenetic Modifications.

Basu, A., Bobrovnikov, D.G., Cieza, B. et al. Deciphering the mechanical code of the genome and epigenome. Nat Struct Mol Biol 29, 1178–1187 (2022). https://doi.org/10.1038/s41594-022-

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