Variety of genomic DNA patterns for nucleosome positioning

Abstract

Precise positioning of nucleosomes along DNA is important for a variety of gene regulatory processes. Among the factors directing nucleosome positioning, the DNA sequence is highly important. Two main classes of nucleosome positioning sequence (NPS) patterns have previously been described. In the first class, AA, TT, and other WW dinucleotides (where W is A or T) tend to occur together (in-phase) in the major groove of DNA closest to the histone octamer surface, while SS dinucleotides (where S is G or C) are predominantly positioned in the major groove facing outward. In the second class, AA and TT are structurally separated (AA backbone near the histone octamer, and TT backbone further away), but grouped with other RR (where R is purine A or G) and YY (where Y is pyrimidine C or T) dinucleotides. As a result, the RR/YY pattern includes counter-phase AA/TT distributions. We describe here anti-NPS patterns, which are inverse to the conventional NPS patterns: WW runs inverse to SS, and RR inverse to YY. Evidence for the biological relevance of anti-NPS patterns is presented.

Figure 1.

Spatial presentation of the various AA, TT nucleosome DNA sequence patterns (scheme). (A) Specific example of AA (or TT). (Left panel) The pattern described by Albert et al. (2007). (Right panel) The “anti” configuration. Note, AA or TT at each indicated position on each strand is allowable. (B) The general case from panel A is shown. Smaller letters for SS indicate a small contribution. The patterns are shown only in the area close to the dyad.

Figure 2.

Spatial presentation of the various nucleosome DNA sequence patterns (scheme). (A) Counter-phase AA/TT (left) and anti-AA/TT (right) patterns. (B) RR/YY (left) and anti-RR/YY (right) patterns. The variable size of the letters reflects variable peak magnitude of respective dinucleotide distributions at subsequent figures (no precise scale was kept). The patterns are shown only in the area close to the dyad.

Figure 3.

Counts for combined dinucleotide distributions (smoothed by 3-points sliding average) for the well-phased H2A.Z nucleosomes used as a training set (according to Albert et al. 2007). Positions are for the aligned nucleosome DNA sequences. Position 0 coincides with the dyad symmetry of the nucleosome. Normalized frequency distributions can be found in Supplemental Figure 2.

Figure 4.

Counts of individual dinucleotides along nucleosomal DNA for the studied nucleosomes from Albert et al. (2007). (A) Individual WW dinucleotides. (B) Individual SS dinucleotides. Vertical lines are drawn through the peaks for AA, TT, and AT dinucleotides that are clearly out of phase.

Figure 5.

Combined dinucleotide distributions (smoothed by 3 points) for subsets with AAs positively correlating with the major WW pattern from Albert et al. (2007) (+, higher in the graph) and with AAs negatively correlating with the major WW pattern (−, lower in the graph).

Figure 6.

Combined dinucleotide distributions (smoothed by 3) for nucleosome subsets with positive (A) and negative (B) AA/TT correlation to the counter-phase AA/TT pattern from Ioshikhes et al. (1996). Notice opposite phases for RR patterns at A and B, for YY patterns at A and B, and steep gradients for RR and WW patterns at A (no obvious gradients at B). The opposite phases for the patterns in the A and B panels are related to inverse positioning of respective sequence elements in conventional (major) patterns and respective anti-patterns (presented in Fig. 2, left and right sides, respectively).

Figure 7.

WW and SS patterns (smoothed by 3) for subsets with positive (+) and negative (−) WW/SS correlation to the major WW/SS patterns from Albert et al. (2007). Notice identical phases for the WW− and SS+ and for the WW+ and SS− patterns.

Figure 8.

Counter-phase AA/TT NPS and anti-NPS correlations predict subsets of nucleosome locations. Regular (black trace) and anti- (red trace) counter-phase AA/TT correlations are shown for composite subsets of nucleosomes defined by K-means clustering (from −500 to +1000 bp) of in vivo patterns for genes aligned by their TSS (Zhang et al. 2011). The gray-filled background shows the composite nucleosome distribution for each cluster of genes.