CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators

article CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators epub_ahead yes Fatih Aygenli author Lukas A. Huschet author Tanja Popp author Andrea Ribeiro author Darina Barkhatova author db547c8c-329f-11ee-a353-cde802618f9e0000-0002-0062-2817 Céline Jouffe author Ricardo Trozzo author Jerome S. Menet author Roland Rad author Kenneth A. Dyar author Maciej Lech author Tobias Straub author Alicia Michael author 6437c950-2a03-11ee-914d-d6476dd7b75c0000-0002-6080-839X Maria S. Robles author GradSch department AlMi department Circadian structural transitions of chromatin project Circadian clocks underlie daily rhythms in physiology by coordinating temporal patterns of gene expression and protein function throughout the body. At the core of this system in mammals is CLOCK/BMAL1, a ubiquitously expressed heterodimeric transcription factor complex that orchestrates tissue-specific circadian gene expression. The basis for this specificity remains unclear, but tissue-specific interactions at chromatin could provide one. Here we used chromatin immunoprecipitation coupled to mass spectrometry to map CLOCK/BMAL1-associated protein complexes on chromatin in mouse liver, kidney and lung. We detected 1,510 associated proteins, most of which were tissue-specific and not explained by protein abundance. Among these, we identified the homeodomain transcription factors PROX1, HNF1B and HOXA5 as tissue-enriched interactors that bind BMAL1, co-occupy most BMAL1 genomic sites and establish organ-restricted circadian transcription. Our findings demonstrate that tissue-specific transcription factors confer cellular identity on the core clock, thereby contributing to organ-specific patterns of rhythmic gene expression. https://creativecommons.org/licenses/by/4.0/ Springer Nature2026 eng Nature Cell Biology 1465-7392 1476-4679 4256292410.1038/s41556-026-02041-4 Aygenli F, Huschet LA, Popp T, Ribeiro A, Barkhatova D, Jouffe C, Trozzo R, Menet JS, Rad R, Dyar KA, Lech M, Straub T, Michael AK, Robles MS. 2026. CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators. Nature Cell Biology. Aygenli, F., Huschet, L. A., Popp, T., Ribeiro, A., Barkhatova, D., Jouffe, C., … Robles, M. S. (2026). CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators. Nature Cell Biology. Springer Nature. <a href="https://doi.org/10.1038/s41556-026-02041-4">https://doi.org/10.1038/s41556-026-02041-4</a> F. Aygenli, L.A. Huschet, T. Popp, A. Ribeiro, D. Barkhatova, C. Jouffe, R. Trozzo, J.S. Menet, R. Rad, K.A. Dyar, M. Lech, T. Straub, A.K. Michael, M.S. Robles, Nature Cell Biology (2026). Aygenli, Fatih, Lukas A. Huschet, Tanja Popp, Andrea Ribeiro, Darina Barkhatova, Céline Jouffe, Ricardo Trozzo, et al. “CLOCK/BMAL1 Interactome Uncovers Homeodomain Factors as Tissue Regulators.” Nature Cell Biology. Springer Nature, 2026. <a href="https://doi.org/10.1038/s41556-026-02041-4">https://doi.org/10.1038/s41556-026-02041-4</a>. Aygenli, Fatih, et al. “CLOCK/BMAL1 Interactome Uncovers Homeodomain Factors as Tissue Regulators.” Nature Cell Biology, Springer Nature, 2026, doi:<a href="https://doi.org/10.1038/s41556-026-02041-4">10.1038/s41556-026-02041-4</a>. F. Aygenli et al., “CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators,” Nature Cell Biology. Springer Nature, 2026. Aygenli F, Huschet LA, Popp T, et al. CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators. Nature Cell Biology. 2026. doi:<a href="https://doi.org/10.1038/s41556-026-02041-4">10.1038/s41556-026-02041-4</a> 227202026-08-16T22:01:44Z2026-08-18T08:03:22Z