Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
A Statistical Thermodynamic Approach for Predicting The Sequence-Dependent Nucleosome Positioning along Genomes
Eukaryotic DNAs are organized as linear arrays of nucleosomes that mutually interact giving rise to the chromatin architecture, which is the substrate for the regulation of nuclear processes. Positioning of the nucleosomes along DNA is the main determinant of their compaction in chromatin. However, although the structure of the nucleosome is known in its molecular details, the basic knowledge about the positioning along genomes is still debated.
Assuming that inter-nucleosomal forces are not effective in perturbing the distribution of nucleosomes along DNA, we tried to predict the nucleosome positioning along genomes extending the theoretical model based on a statistical mechanical approach we early proposed. It allowed the calculation of the free energies involved in nucleosome formation for about hundred single nucleosome DNA tracts in satisfactory agreement with those experimentally obtained in different laboratories with the nucleosome competitive reconstitution (see figure A). To test the model, the theoretical free energy profile was compared with the experimental positioning data of yeast chromosomes available in literature (see figure B as an example). The results are comparable with those obtained by different authors adopting models based on identifying of some recurrent sequence signals obtained from the statistical analysis of a very large pool of nucleosomal DNA sequences provided by the positioning maps of genomes. Aside its effectiveness in predicting the nucleosome positioning along genomes, our model provides the basic physical knowledge of the main determinants of the nucleosome thermodynamic stability along genomic DNAs.
P. De Santis
Dipartimento di Chimica