Colocalized binding of clock- and liver-specific TFs underlies liver-specific mRNA rhythms. (A) The fraction of genes containing liver-specific DNase I hypersensitive sites (DHSs) in the clock-driven liver-specific module is higher compared with both nonrhythmic and system-driven liver-specific modules. Error bars and P-values calculated from 10,000 bootstrap iterations. (B) Predicted temporal activities of RORE (top) and E-box (bottom) TF motifs located within liver-specific DHSs. Error bars show standard deviation of the estimated activities. (C) Co-occurrence of RORE with all other TFs in the SwissRegulon database (Pachkov et al. 2007) (189 TF motifs). Positive log₁₀ odds ratios (ORs) represent pairs of motifs enriched in the clock-driven liver-specific module compared to the flat module. P-values for the motif pairs were calculated from χ² tests applied to three-way contingency tables (Myšičková et al. 2012). Selected pairs are in bold. (D) DNase I hypersensitivity in liver, kidney, and the corresponding differential signal (in log₂ fold change) near two representative genes (top: Insig2; bottom: Slc4a4). RORE, ONECUT1, and FOXA2 TF binding motifs (posterior probability > 0.5, MotEvo) co-occur at liver-specific DHSs (red boxes). Predicted TF binding sites correspond to experimentally observed TF binding in publicly available ChIP-exo data sets for REV-ERBa, ONECUT1, and FOXA2 (bottom).