Preferential nucleosome occupancy at high values of DNA helical rise

Abstract

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. A reference data set of positioned nucleosomes of Saccharomyces cerevisiae was used to study the role of DNA helical rise in histone-DNA interaction. Genomic sequences were transformed into arrays of helical rise values by a tetranucleotide code and then turned into profiles of mean helical rise values. These profiles resemble maps of nucleosome occupancy, suggesting that intrinsic histone-DNA interactions are linked to helical rise. The obtained results show that preferential nucleosome occupancy occurs where the mean helical rise reaches its largest values. Mean helical rise profiles obtained by using maps of positioned nucleosomes of the Drosophila melanogaster and Plasmodium falciparum genomes, as well as Homo sapiens chromosome 20 confirm that nucleosomes are mainly located where the mean helical rise reaches its largest values.

Figure 1.

Helical rise profiles of nucleosome positions. (A) Average helical rise profiles of mapped nucleosome positions in yeast (average of 61 110 points, black solid line) and in an isw2 deletion strain (average of 54 907 points, pink solid line) for four different smoothing windows of 26, 56, 90 and 150 bp. (B) Average helical rise profiles of mapped nucleosome positions in chromosome I of yeast (average of 1183 points, black solid line), in an isw2 deletion strain (average of 1069 points, pink solid line) and in scrambled nucleosome positions in chromosome I of yeast (average of 1183 points, grey solid line) with a smoothing window of 56 bp. Nucleosome dyad positions are aligned at bp number 0; 500 bp upstream and downstream of this point are shown. Black dots with (146-bp long) horizontal bars mark positions of mapped nucleosomes. Colour figures can be found in the online version of this paper.

Figure 2.

Peak height analysis of nucleosome positions. Average helical rise profiles of mapped nucleosome positions in yeast for a 90-bp smoothing window. Average of 24 600 points with a peak height >4 (red solid line); of 29 800 points with a peak height <4 and >2 (green solid line); of 5600 point with a peak height <2 (blue solid line); of 61 110 points previously shown in Fig. 1A with a 90-bp smoothing window (black solid line). Black dots with (146-bp long) horizontal bars mark positions of mapped nucleosomes. Colour figures can be found in the online version of this paper.

Figure 3.

Helical rise profiles of nucleosome positions at promoters. (A) Helical rise profile (black solid line) of the YAL053W promoter sequence in chromosome 1 of S. cerevisiae, obtained by a smoothing window of 90 bp. Nucleosome occupancy profile (pink solid line) obtained by the dinucleotide frequency method by Segal et al. Upper black dots with horizontal bars return peak heights of the corresponding nucleosomes. Lower black dots with horizontal bars return nucleosome numbering. Blue dots with horizontal bars return nucleosome repositioning in the isw2 deletion strain. Green and red dots represent TSS and TTS, respectively. (B) Helical rise profile (black solid line) of YAL053W smoothed at 90 bp as in (A). Average helical rise profiles (red solid lines) for nucleosomes sharing the same position number. Upper red dots with horizontal bars return mean peak heights of the corresponding nucleosomes expressed in arbitrary units as reported in the ‘additional data file 1’. Lower black dots with horizontal bars return nucleosome numbering. Green and red dots represent TSSs and TTSs, respectively. (C) Scale enlargement of the mean helical rise profiles for nucleosomes sharing the same position number reported in (B, black solid line). The mirror image of the same profiles (pink solid line). The average between peak heights of the black and pink profiles (blue diamonds). Black dots with horizontal bars return nucleosome numbering. Colour figures can be found in the online version of this paper.

Figure 4.

Helical rise profiles of nucleosome positions of various genomes. Average helical rise profiles of experimentally mapped nucleosome positions in D. melanogaster (A, average of 617 304 points, black solid line), P. falciparum (B, average of 89 115 points, black solid line), chromosome 20 of human genome (C, average of 65 379 points, black solid line) and in computationally mapped nucleosome positions in chromosome 20 of human genome (D, average of 65 537 points, dinucleotide frequency method, grey solid line and average of 65 537 points, curvature profile method, black solid line). All the curves were obtained with smoothing windows of 56 bp. Nucleosome dyad positions are aligned at bp number 0; 500 bp upstream and downstream of this point are shown. Black dots with (146-bp long) horizontal bars return the position of the central nucleosome.

Figure 5.

Helical rise and GC content. The helical rise values of the 136 unique tetranucleotides are shown divided according to their GC content.