Nature Cell Biology, Published online: 06 August 2026; doi:10.1038/s41556-026-02041-4 Aygenli et al. map chromatin-bound CLOCK/BMAL1 protein complexes across three mouse tissues and uncover PROX1, HNF1B and HOXA5 as homeodomain cofactors that directly bind and co-occupy BMAL1 sites to establish tissue-specific circadian transcription.