The mechanical code of DNA links DNA bending nucleosome organization and codon choice

Nucleosomes are the fundamental units of chromatin, yet how DNA sequence encodes the mechanics required for their formation remains incompletely understood. Using high-throughput measurements and predictive modeling, we show that nucleosomal DNA is distinguished not only by enhanced isotropic bendability but by coherent anisotropic bending aligned with the DNA helical repeat. Within nucleosome footprints, anisotropy vectors are phase-aligned across thousands of sequences, yielding ensemble-level signatures—such as ∼15 full rotations of bending direction—that directly mirror histone–DNA wrapping. We show that within nucleosomes, reinforcement of bending direction every helical repeat pre-disposes DNA to wrap smoothly around histones, lowering the energetic cost of nucleosome formation. Extending these principles to coding regions, we demonstrate that synonymous codon usage bias varies systematically around nucleosomes in a manner that optimizes DNA mechanical and structural features around nucleosomes and suggest that degeneracy of the genetic code has been exploited to encode both proteins and chromatin architecture. Together, our findings establish DNA anisotropy as a pervasive, sequence-encoded feature of nucleosomal DNA and identify codon usage as a key contributor to this hidden mechanical code.