Abstract
BackgroundNucleosomes are the basic structural units of eukaryotic chromatin and play a key role in regulation of gene expression. After resolution of the nucleosome structure, the bipartite nature of this particle has revealed itself and has disclosed the presence, on the histone surface, of a symmetric distribution of positive charges, able to interact with their negative DNA phosphate counterpart.ResultsWe analyzed helical steps in known nucleosomal DNA sequences, observing a significant relationship between their symmetric distribution and nucleosome stability. Synthetic DNA sequences able to form stable nucleosomes were used to compare distances on the left and on the right side of the nucleosomal dyad axis, where DNA phosphates and charged residues of the (H3H4)2-tetramer interact. We observed a linear relationship between coincidence of distances and nucleosome stability, i. e., the more symmetric these distances the more stable the nucleosome.ConclusionCurves related to this symmetric distribution along the DNA sequence identify preferential sites for positioning of the dyad axis, which we termed palinstases. The comparison of our data with known nucleosome positions in archaeal and eukaryotic sequences shows many coincidences of location. Sequences that impair nucleosome formation and DNase I hypersensitive sites yield curves with a lower degree of symmetry. Analysis performed on DNA tracts of promoters close to the transcription start and termination sites identified peculiar patterns: in particular low affinity for nucleosome binding at the transcription start site and a high affinity exactly at the transcription termination site, suggesting a major role of nucleosomes in the termination of transcription.
Highlights
Nucleosomes are the basic structural units of eukaryotic chromatin and play a key role in regulation of gene expression
Curves related to this symmetric distribution along the DNA sequence identify preferential sites for positioning of the dyad axis, which we termed palinstases
Analysis performed on DNA tracts of promoters close to the transcription start and termination sites identified peculiar patterns: in particular low affinity for nucleosome binding at the transcription start site and a high affinity exactly at the transcription termination site, suggesting a major role of nucleosomes in the termination of transcription
Summary
Nucleosomes are the basic structural units of eukaryotic chromatin and play a key role in regulation of gene expression. After resolution of the nucleosome structure, the bipartite nature of this particle has revealed itself and has disclosed the presence, on the histone surface, of a symmetric distribution of positive charges, able to interact with their negative DNA phosphate counterpart. The role played by the DNA sequence in determining preferred positions of individual nucleosomes has been studied using both experimental and theoretical approaches. The histone particle presents, on its surface, a distribution of positive charges able to interact with their negative DNA phosphate counterpart. These charges are symmetrically distributed with respect to the pseudo-dyad axis of the nucleosome and constitute a 'mask' of distances that remained constant during evolution [18]. We observed that DNA oligomers having the same number of base pairs, as reported in X-ray and NMR databases, show different lengths, i.e., the length of dodecamers varies from 32 up to 37Å
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