Fig. 4: Contribution of ligand- and partner proteins on RXRA binding site preferences.
From: Hidden modes of DNA binding by human nuclear receptors
a LOGO representation of DNA-binding preferences of RXRA with and without its ligand (#17) for different orientations of 5ʹRGKTCR3ʹ half site separated by different spacer lengths (n1–n7). b Specificity and binding-energy landscapes (SELs) of an example case with 5ʹNRGGTCR-n1-RGGTCRN3ʹ direct repeat as a seed to organize (where R = A/G, N = A/C/G/T, n = spacer). The top panel displays a histogram of enriched k-mers, with the highest affinity k-mers used to derive a position weight matrix-based motif (DR1). The color scale represents the extent of enrichment/affinity. In circular SELs, (second panel), the PWM motif is used as a seed to organize the rest of the k-mers in concentric circles. The central ring contains all k-mers that match the seed 5’NRGGTCR-n-RGGTCRN3’ motif but may differ in spacer and flanking sequences. Sequences with a hamming distance m from this motif are represented in corresponding mth (0,1, 2,…) mismatch rings. Color-coded enrichment values are proportional to the binding affinities of individual k-mers and variations in intensity reflect the contribution of the spacer and flanking sequences on binding to the core motif (third panel from the top). In the bottom panel, central rings (no mismatch to the motif) of SELs are linearized along the y-axis in the direction of the dotted arrow and arrayed along the x-axis by increasing increments in the intervening spacer length (n0–8). c Linear-SELs depict the effects of ligand and partnering RXRA on the binding preference of selected NRs. Along the x-axis in the left panel, the half-site is presented as a direct repeat (DR) with spacer n spanning 0–8 base pairs. The middle and right panels display the same half-site in an inverted (IR 0-8) or everted (ER 0-8) arrangement. Half-site is 5ʹRGKTCR3ʹ for COUP-TF2 and COUP-TF2:RXRA and 5ʹRGGTCR3ʹ for the rest. On the y-axis, k-mers belonging to specific groups (DR, IR, or ER) but bearing different spacer and flanking sequences are plotted in positional and alphabetical order. The z-axis displays the enrichment values of each k-mer as color-coded peaks. For additional details on SELs, see Supplementary Fig. 8. (Source data are provided as a Source Data file. Designed by Laura Vanderploeg).
