Deciphering the mechanical code of the genome and epigenome

Area of Science:

• Molecular Biology
• Biophysics
• Genomics

Background:

• DNA's mechanical and structural properties influence diverse DNA-deforming processes.
• Understanding the mechanical code, which links DNA properties to sequence and epigenetic modifications, has been hindered by a lack of high-throughput experimental methods.

Purpose of the Study:

• To comprehensively characterize the DNA mechanical code.
• To quantitatively establish how DNA sequence and methylation impact DNA bendability.
• To develop and validate a physical model for DNA bendability.

Main Methods:

• Utilized high-throughput loop-seq measurements to assess DNA bendability.
• Quantitatively analyzed the impact of dinucleotides, tetranucleotides, and methylated CpG on DNA bendability.
• Developed a physical model based on experimental measurements.

Main Results:

• Established quantitative relationships between DNA sequence, methylation, and bendability.
• Validated the physical model using genomic sequences from mouse transcription start and CTCF-binding sites.
• Demonstrated that sequence and epigenetic modifications mechanically encode regulatory information.

Conclusions:

• The study presents a comprehensive characterization of the DNA mechanical code.
• The developed physical model accurately predicts DNA bendability based on sequence and methylation.
• This work provides insights into how DNA mechanically encodes regulatory information in various genomic contexts.