Investigating the Interplay between Nucleoid-Associated Proteins, DNA Curvature, and CRISPR Elements Using Comparative Genomics

Hao Tong, Jan Mrázek

Many prokaryotic and eukaryotic genomes feature a characteristic periodic signal in distribution of short runs of A or T (A-tracts) phased with the DNA helical period of ∼10-11 bp. Such periodic spacing of A-tracts has been associated with intrinsic DNA curvature. In eukaryotes, this periodicity is a major component of the nucleosome positioning signal but its physiological role in prokaryotes is not clear. One hypothesis centers on possible role of intrinsic DNA bends in nucleoid compaction. We use comparative genomics to investigate possible relationship between the A-tract periodicity and nucleoid-associated proteins in prokaryotes. We found that genomes with DNA-bridging proteins tend to exhibit stronger A-tract periodicity, presumably indicative of more prevalent intrinsic DNA curvature. A weaker relationship was detected for nucleoid-associated proteins that do not form DNA bridges. We consider these results an indication that intrinsic DNA curvature acts collaboratively with DNA-bridging proteins in maintaining the compact structure of the nucleoid, and that previously observed differences among prokaryotic genomes in terms DNA curvature-related sequence periodicity may reflect differences in nucleoid organization. We subsequently investigated the relationship between A-tract periodicity and presence of CRISPR elements and we found that genomes with CRISPR tend to have stronger A-tract periodicity. This result is consistent with our earlier hypothesis that extensive A-tract periodicity could help protect the chromosome against integration of prophages, possibly due to its role in compaction of the nucleoid.