A study of the impact of DNA helical rise on protein-DNA interaction.

Nucleosomes are not uniformly distributed along DNA and their positioning (termed "nucleosomal landscape") can be derived using data available for several genomes. In this study we analyzed DNA helical rise profiles through a tetranucleotide code, and we defined the nucleosomal landscape of several sequences forming dinucleosomes and of the sequences of huntingtin, myotonic dystrophy type 1 and fragile mental retardation 2 genes, which contained several repeated sequences. We also analyzed the profiles of some sequences interacting with transcription factors or with RNA polymerase II.

Preferential nucleosome occupancy at high values of DNA helical rise.

Nucleosomes are the basic structural units of eukaryotic chromatin and play a key role in the regulation of gene expression. Nucleosome formation depends on several factors, including properties of the sequence itself, but also physical constraints and epigenetic factors such as chromatin-remodelling enzymes. In this view, a sequence-dependent approach is able to capture a general tendency of a region to bind a histone octamer.

Sequence-dependent DNA helical rise and nucleosome stability.

Background: 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.

Results: We analyzed helical steps in known nucleosomal DNA sequences, observing a significant relationship between their symmetric distribution and nucleosome stability.

Sequence-dependent DNA torsional rigidity: a tetranucleotide code.

Using fluorescence polarization anisotropy (FPA), we measured the torsional constant of various DNA oligomers in different sequences and calculated the value for each of the 136 unique tetranucleotides. From these values, we obtained a "rigidity profile" for every double-stranded DNA sequence. We tested the code in the analysis of DNA sequences able to form nucleosomes.

Torsional constant of 27-mer DNA oligomers of different sequences.

We have studied the torsional elastic constant (alpha) of short DNA (27mer) oligomers of various sequence by fluorescence polarization anysotropy (FPA) measurements. The lowest alpha values were found in samples with sequence rich in AA dinucleotides or containing the alternating d(A-T) x d(A-T) motif. The torsional rigidity of our DNA samples was compared to that calculated according to the current values of twist angle fluctuations derived for ten dinucleotide steps by recent analyses of DNA crystal structure database.