Mechanical deformations of DNA are ubiquitously part of universal biological processes involved in the transduction of genetic information. Although the average compliance of DNA to accommodate such deformations has been extensively measured, biophysical measurements of DNA have never been conducted on a genome-wide scale. Consequently, we lack experimental understanding of the extent to which the local mechanical properties of DNA vary with sequence along entire genomes, and how such variations modulate the energetics of diverse biological processes.