Liver-specific chromatin loops regulate liver-specific mRNA rhythms. (A) Temporal mRNA profile for Mreg, a clock-driven liver-rhythmic gene. Error bars are SEM (n = 2). (B) 4C-seq profiles (summary from two replicates, each pooling two different mice) using the Mreg promoter as a bait in liver and kidney at ZT20. Data are shown in a window of ±250 kb from the bait (top). Profiles of differential contacts between liver and kidney (bottom) represented as signed log P-values (regularized t-test, positive values denote liver-enriched 4C contacts). (C) Tracks of differential 4C contacts (signed log P-values), log₂ fold change of DNase I hypersensitivity between liver and kidney, and ChIP-exo of REV-ERBa and FOXA2. Regions of significant differential 4C contacts correspond to liver-specific DNase I hypersensitive regions and REV-ERBa binding sites.