Book of Abstracts: Albany 2003
June 17-21 2003
Genome-wide A-tract Distribution and DNA Packaging in Pro- and Eukaryotes
Periodic positioning of the A-tracts in DNA causes DNA curvature in solution and facilitates its bending in the complexes with proteins. A-tracts are the sequence motifs AmTn, the strongest DNA curvature in solution being observed for m+n = 4 to 7. Here, we analyzed the distribution of these sequences in the pro- and eukaryotic genomes (E.coli, S.typhimurium, B.subtilus and H.sapiens).
We found that the ?optimal? A-tracts (4-7 bp) are overrepresented, while the longer A-tracts are underrepresented in bacterial genomes. Distribution of the ?optimal? A-tracts in the prokaryotic genomes showed a remarkable periodicity of 10-11 bp. Since the A-tracts separated by 10-11 bp produce significant DNA curvature, such a periodicity may reflect the intrinsic propensity of prokaryotic DNA to form the loop-shaped structures. Both coding and non-coding DNA regions demonstrate the bending propensities due to the A-tracts, with the largest bends in the non-coding regions, e.g. promoters, as compared to a random sequence of the same GC content. Based on these data and by analogy with the DNA looping in repressosome strucutures in the E. coli gal and lac operons (1), we hypothesized that the loop folds with a structural period of ~100 bp can be elementary units of the prokaryotic nucleoid packaging (with the promoters located near the loop apexes). The hypothesis was tested by limited micrococcal nuclease digestion of bacterial nucleoids. The results obtained and observed previously (2) showed that DNA fragments ~100 bp in lengths are highly overrepresented among the digestion products. This implies specific nucleoid packaging, with a DNA structural period of ~100 bp.
The A-tracts of all lengths are highly overrepresented in eukaryotic genomes. At the same time, the ?optimal? A-tracts (4-7 bp) do not reveal a 10-11 bp periodicity. Apparently, the intrinsic curvature of DNA, caused by the A-tracts, is not a prerequisite for the formation of nucleosomes. Rather, the overabundant long purine runs observed in eukaryotic genomes may serve as the ?chromatin organizers,? decreasing the DNA propensity for the formation of nucleosomes.
In summary, we suggest that the nonrandom distributions of the A-tracts in pro- and eukaryotic genomes play different roles in DNA packaging and regulation of gene expression.
1Laboratory of Experimental and Computational Biology