Loop-seq: A high-throughput technique to measure the mesoscale mechanical properties of DNA

The local mechanical properties of the DNA polymer influence molecular processes in biology that require mechanical deformations of DNA. Lack of suitable high-throughput experimental techniques had precluded measuring how these properties might vary with sequence along the vast lengths of genomes. Here, we present a detailed protocol for a recently developed experimental technique called loop-seq, which measures at least one local mechanical property of DNA-its propensity to cyclize-in genome-scale throughput. Loop-seq has been used to obtain experimentally derived genome-wide maps of a physical property of DNA. Such measurements have revealed that diverse DNA-deforming processes involved in chromatin organization at various genomic loci are regulated by the genetically encoded, sequence-dependent variations in the mechanical properties of DNA.