Book of Abstracts: Albany 2005

category image Volume 22
No. 6
June 2005

A-tract Clustering, DNA Looping, and Bacterial Genome Packaging

Molecular mechanisms of the bacterial genome packaging are still unclear, as bacteria appear to lack nucleosomes. Among the factors facilitating DNA condensation may be a propensity of the DNA molecule to fold due to its intrinsic curvature. It was suggested previously that the sequence correlations in genome might bring about such a propensity (1). To further elaborate this concept, we analyzed the distribution of A-tracts (the sequence motifs AmTn introducing the most pronounced DNA curvature) in the genomes of E. coli and several other bacteria.

We observed that: (i) A-tracts are over-represented and distributed ?quasi-regularly? in bacterial genomes of the intermediate GC-content (40-60% [G+C]); (ii) there is a 10-12 bp periodicity in the A-tract positioning indicating that A-tracts are phased with respect to the DNA helical repeat; (iii) the phased A-tracts are organized in ∼100 bp long clusters (this feature was revealed with the help of a novel approach based on the Fourier series expansion of the A-tract distance autocorrelation function); (iv) the clusters of phased A-tracts are abundant both in coding and in intergenic regions of the genomes (Figure 1).

Figure 1: Distribution of the A-tract curvature in the E. coli genome (red ? CDS, black ? intergenic sequences). The numbers on the outmost circle indicate the position in the genome in millions of base pairs. The A-tract curvature, calculated in the 'sliding' 100 bp window, varies from 40° (innermost circle) to 150° (outmost circle). Notice that the strong peaks in A-tract curvature (up to 100°) are located both in the intergenic regions and in the CDS.

The observed clusters would facilitate DNA looping since the A-tracts introduce local bends of the DNA duplex and these bends accumulate if properly phased. Also, such clusters may serve as binding sites for the nucleoid-associated proteins that have affinities for curved DNA (such as HU, H-NS, Hfq, CbpA). Remarkably, the MNase digestion experiments indicate that abundant structural components of E. coli nucleoid contain 100-120 bp DNA fragments (2). This size is also very close to the size of the regulatory gal- and lac- loops (113 and 92 bp respectively). We suggest that the ∼100 bp clusters of phased A-tracts constitute a ?structural code? for DNA folding by providing the long-range intrinsic curvature and increasing the stability of DNA loops.

References and Footnotes
  1. Trifonov, E. N. and Sussman, J. L. Proc. Natl. Acad. Sci. USA 77, 3816-3820 (1980).
  2. Varshavsky, A., Nedospasov, S., Bakayev, V., Bakayeva, T., and Georgiev, G. Nucleic Acids Res. 4, 2725-2745 (1977).

Michael Y. Tolstorukov1,*
Konstantin M. Virnik2
Sankar Adhya2
Victor B. Zhurkin1

1Laboratory of Experimental and Computational Biology
2Laboratory of Molecular Biology
National Cancer Institute
Bethesda, MD 20892

*Phone: (301) 496 8913
Fax: (301) 402 4724
Email: tolstorukov@yahoo.com