Structural Insight into the Sequence Dependence of Nucleosome Positioning

SummaryNucleosome positioning displays sequence dependency and contributes to genomic regulation in a site-specific manner. We solved the structures of nucleosome core particle composed of strong positioning TTTAA elements flanking the nucleosome center. The positioning strength of the super flexible TA dinucleotide is consistent with its observed central location within minor groove inward regions, where it can contribute maximally to energetically challenging minor groove bending, kinking and compression. The marked preference for TTTAA and positioning power of the site 1.5 double helix turns from the nucleosome center relates to a unique histone protein motif at this location, which enforces a sustained, extremely narrow minor groove via a hydrophobic “sugar clamp.” Our analysis sheds light on the basis of nucleosome positioning and indicates that the histone octamer has evolved not to fully minimize sequence discrimination in DNA binding.

Graphical AbstractFigure optionsDownload high-quality image (411 K)Download as PowerPoint slideHighlights
► TA dinucleotides optimal for histone-imposed minor groove deformation/structure
► Histone-imposed minor groove narrowness is site dependent
► Conserved histone motif yields nucleosome translational positioning mechanism
► Histone octamer has evolved not to fully minimize DNA sequence discrimination