Abstract
In recent decades, study of DNA structure has largely been focused on the interrelationships between nucleotides at the level of nearest neighbours. A little-utilized approach to probing structure on a larger scale is non-denaturing bisulfite modification of genomic DNA in conjunction with high-throughput sequencing. This technique revealed a marked gradient in reactivity increasing towards the 5 ' end of poly-dC:dG mononucleotide repeats as short as two base pairs, suggesting that access of the anion may be greater at these points due to positive-roll bending not predicted by existing models. Consistent with this, the 5 ' ends of these repeats are strikingly enriched at positions relative to the nucleosome dyad that bend towards the major groove, while their 3 ' ends tend to sit outside these areas. Mutation rates are also higher at the 5 ' ends of poly-dC:dG when CpG dinucleotides are excluded. These findings shed light on the mechanisms underlying bending/flexibility of the DNA double helix as well as the sequences that facilitate DNA packaging.