Figure 3.
Elastic energy analysis of the nucleosome crystal structure. (a) Position-dependent sequence specificity in the nucleosomal DNA revealed by the energetic analysis of dinucleotides substituted into the crystal structure of the nucleosome core particle [PDB code: 1kx5; (2)] All possible dinucleotides were introduced at every position into the 147 bp nucleosomal site using DNA dihedral angles from the native dinucleotide, and DNA elastic energy was computed for every sequence variant. Upper panel: the difference between the energy of the most favorable dinucleotide and the average energy of all dinucleotides at this position. Lower panel: information entropy, defined as 
, where 
, and Eis is the elastic energy change which results from introducing a dinucleotide of type i = 1, … , 16 at position s: Eis = Eis(mut) − Eis(wt). To enforce the 2-fold symmetry of the nucleosome core particle, all dinucleotide energies were symmetrized around the middle of the DNA site, shown as a dashed vertical line. Middle panel: roll angle of the ideal superhelix showing DNA geometry in relation to the histone octamer. Negative roll angles correspond to the minor groove facing the histone surface. (b) Elastic energy components for all possible dinucleotides substituted into the 1kx5 crystal structure at position 109 where the DNA conformation is kinked (Figure 2) (2). Dinucleotides are ranked by their total energy as shown in the legend (best to worst energy from top to bottom). TA is the lowest energy dinucleotide (thick golden line). The energy component analysis reveals that it is the degrees of freedom related to slide (slide–slide and slide–twist components) and roll (roll–roll component) that make the TA dinucleotide most favorable, although the slide–slide component is slightly better in the native CA/TG dinucleotide (red/brown dots). In contrast, the AT dinucleotide (black lines) has the highest energy due to its low flexibility with respect to roll, slide and twist (Supplementary Table 2).