Measuring DNA mechanics on the genome scale.

Area of Science:

• Molecular Biology
• Genomics
• Biophysics

Background:

• DNA mechanical properties, like bending, are crucial for cellular functions but are difficult to measure at scale.
• Understanding DNA mechanics is key to deciphering chromatin transactions and genome-wide regulation.

Purpose of the Study:

• To develop a high-throughput assay (loop-seq) for measuring DNA looping propensity and intrinsic cyclizability.
• To map DNA mechanics across a large genomic scale and identify sequence-encoded mechanical properties.

Main Methods:

• Developed 'loop-seq', a high-throughput assay to quantify DNA looping propensity.
• Analyzed 270,806 50-bp DNA fragments from Saccharomyces cerevisiae chromosome V, other genomic regions, and random sequences.
• Correlated DNA mechanics with nucleosome positioning, chromatin remodeler activity, and transcription start sites.

Main Results:

• Identified sequence-encoded regions of low DNA bendability upstream of transcription start sites (TSSs).
• Demonstrated that low bendability of linker DNA inhibits nucleosome sliding by the INO80 chromatin remodeler.
• Revealed distinct DNA bendability patterns in nucleosomes (high at dyads, low at linkers) influenced by codon choice and affecting transcription.

Conclusions:

• A genome-scale map of DNA mechanics reveals a 'mechanical code' influencing fundamental biological processes.
• DNA mechanics play a significant role in defining nucleosome-depleted regions and regulating gene expression.
• The evolution of codon choice may be shaped by the mechanical properties of DNA within nucleosomes.