Our results suggest that large-scale yeast nuclear architecture can be largely understood as a consequence of generic properties of crowded polymers rather than of specific DNA-binding factors and that configurations of chromosomes and DNA contacts are dictated mainly by genomic location and chromosome lengths. Our model provides a quantitative framework to understand and predict large-scale spatial genome organization and its interplay with functional processes.

Using magnetic tweezers to investigate the mechanical response of single chromatin fibers, we show that fibers submitted to large positive torsion transiently trap positive turns at a rate of one turn per nucleosome. A comparison with the response of fibers of tetrasomes (the [H3-H4](2) tetramer bound with approximately 50 bp of DNA) obtained by depletion of H2A-H2B dimers suggests that the trapping reflects a nucleosome chiral transition to a metastable form built on the previously documented right-handed tetrasome. In view of its low energy, <8 kT, we propose that this transition is physiologically relevant and serves to break the docking of the dimers on the tetramer that in the absence of other factors exerts a strong block against elongation of transcription by the main RNA polymerase.