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. 2011 Dec 16;6(12):1314-20.
doi: 10.1021/cb200155t. Epub 2011 Oct 13.

A map of minor groove shape and electrostatic potential from hydroxyl radical cleavage patterns of DNA

Eric P Bishop, Remo Rohs, Stephen C J Parker, Sean M West, Peng Liu, Richard S Mann, Barry Honig, Thomas D Tullius

A map of minor groove shape and electrostatic potential from hydroxyl radical cleavage patterns of DNA

Eric P Bishop et al. ACS Chem Biol. .

Abstract

DNA shape variation and the associated variation in minor groove electrostatic potential are widely exploited by proteins for DNA recognition. Here we show that the hydroxyl radical cleavage pattern is a quantitative measure of DNA backbone solvent accessibility, minor groove width, and minor groove electrostatic potential, at single nucleotide resolution. We introduce maps of DNA shape and electrostatic potential as tools for understanding how proteins recognize binding sites in a genome. These maps reveal periodic structural signals in yeast and Drosophila genomic DNA sequences that are associated with positioned nucleosomes.

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Figures

Figure 1
Figure 1
Quantitative correlation of hydroxyl radical cleavage with DNA structure. (a) H4' (blue) and H5', H5" (red) are the deoxyribose hydrogen atoms most often abstracted by the hydroxyl radical. (b) The extent of hydroxyl radical cleavage (black circles) at each of the 10 interior nucleotides of the Drew-Dickerson dodecamer is compared to the sum of the solvent accessible surface area (SASA) of the 4', 5', and 5" hydrogen atoms of that nucleotide (red diamonds). (These data points represent the sum of the SASAs of the blue and red deoxyribose hydrogen atoms that are shown in (a)). Two backbone deoxyriboses in different structural environments are highlighted in the insets (top). A wide minor groove results in high SASA and hydroxyl radical cleavage (left); a narrow groove is associated with low SASA and cleavage. The Pearson correlation for comparison of the hydroxyl radical cleavage pattern and SASA in Figure 1, panel b is 0.865 (p-value = 0.00123).
Figure 2
Figure 2
(a) Quantitative correlation of the experimental ORChID2 cleavage pattern (black circles), with electrostatic potential (red diamonds) and minor groove width (green squares) determined from a set of five NMR structures of the Drew-Dickerson dodecamer. The Pearson correlation for comparison of the ORChID2 pattern with minor groove width (7 nucleotide positions) is 0.9917 (p-value = 1.21 × 10−5); for comparison of ORChID2 with electrostatic potential (7 positions), 0.868 (p-value = 0.01). (b) Quantitative correlation of the experimental ORChID2 cleavage pattern (black circles), with electrostatic potential (red diamonds) and minor groove width (green squares) determined from eight X-ray structures of the Drew-Dickerson dodecamer. Minor groove width and electrostatic potential are symmetrized to reflect the symmetry of the Drew-Dickerson sequence. The Pearson correlation for comparison of the ORChID2 pattern with minor groove width (7 positions) is 0.997 (p-value = 7.27 × 10−7); for comparison of ORChID2 with electrostatic potential (7 positions), 0.881 (p-value = 8.67 × 10−3).
Figure 3
Figure 3
ORChID2 nucleosome patterns in yeast and fly. Mean ORChID2 values at each nucleotide position of 23,076 yeast (a) and 25,654 fly (b) nucleosome sequences (blue lines) are compared with ORChID2 values for shuffled versions of the same sequences (gray). Minor groove width measurements from nucleosome X-ray structures 1KX5 and 2PYO (Supplementary Figure 4) were aligned by dyad center to the ORChID2 patterns from panels a and b, respectively, and plotted for yeast (c) and fly (d). There is a significant correlation of the ORChID2 value with minor groove width for both yeast and fly nucleosome-bound sequences (inset, panels c and d). (e) Yeast and fly nucleosome sequences have significantly different G/C content distributions (P < 2.2 × 10−16; Wilcoxon rank sum test), but their overall ORChID2 patterns are highly correlated (f). All correlation plots (panels c, d, f) are based on one-half of the nucleosome dyad and are center-aligned by the dyad axis. Gray shading indicates the standard error around the best-fit line.
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