ChIP-seq analyses across diverse murine tissues. (A) Percentage of Rxrα binding sites shared with Rnap2 (blue), Ctcf (red) or both Rnap2 and Ctcf (purple) in liver (L), brain (B), small intestine (I) and skeletal muscle (M). Rxrα binding sites that do not colocalize with Rnap2 and Ctcf are shown in yellow. (B) Analysis of shared binding sites for Rnap2, Rxrα, and Ctcf between all pairwise tissue comparisons. The two tissues utilized for each comparison are given on the x axis. Shared binding sites are shown in black while tissue-specific sites are in green. (C) ChIP-seq raw sequencing read enrichments for Rnap2 at distinct genes illustrate tissue specificity of gene expression. Gene names and window sizes are given above. (D) Canonical motif genomic evolutionary rate profiling (GERP) scores at tissue-specific binding sites (dark red) and binding sites shared by two (red) or more (orange) tissues. The corresponding motif sequence is shown above the graph. GERP scores are significantly higher within bound Rxrα motifs relative to positions that are not within a motif but are within 250 bp of a binding site summit (P < 2.2 × 10-16, one-sided t test); further, there is a highly significant correlation between GERP score and position-specific motif dependencies on a particular nucleotide, with less degenerate positions being more highly conserved (P < 2.2 × 10-16, simple linear regression between GERP scores and the maximum individual nucleotide score at each position in the Rxrα motif position-specific weight matrix).