[{"_id":"22720","supplementarymaterial":"yes","article_type":"original","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41556-026-02041-4"}],"year":"2026","pmid":1,"das_tickbox":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"date_created":"2026-08-16T22:01:44Z","has_accepted_license":"1","OA_type":"hybrid","doi":"10.1038/s41556-026-02041-4","publication":"Nature Cell Biology","language":[{"iso":"eng"}],"publisher":"Springer Nature","date_updated":"2026-08-18T08:03:22Z","abstract":[{"text":"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.","lang":"eng"}],"publication_status":"epub_ahead","ddc":["570"],"quality_controlled":"1","PlanS_conform":"1","tmp":{"short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"scopus_import":"1","acknowledgement":"We thank all members of the Robles’ group for critical comments on and edits to this paper. We thank S. Kay for providing dihXY HCC cell lines and D. Firsov and Y. Bignon for mouse BMAL1-knockout (KO) kidney tissues. This work was supported by the German Research Foundation (DFG) project no. 213249687—SFB 1064 and RO 5675/1-1 to M.S.R., F.A. and L.A.H. M.S.R was also supported by DFG INST 86/1800-1 FUGG and LMU Munich’s Institutional Strategy LMU excellent within the framework of the German Excellence Initiative. J.S.M. was supported by US National Institutes of Health grant nos. R01GM145737 and R01DK128133. A.K.M. was supported by an ERC grant ‘ChromaChrono’ 101162145. Open access funding provided by Ludwig-Maximilians-Universität München.","external_id":{"pmid":["42562924"]},"project":[{"name":"Circadian structural transitions of chromatin","_id":"9136c684-16d5-11f0-9cad-91c0177b365f","grant_number":"101162145"}],"OA_place":"publisher","publication_identifier":{"eissn":["1476-4679"],"issn":["1465-7392"]},"title":"CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators","type":"journal_article","author":[{"first_name":"Fatih","last_name":"Aygenli","full_name":"Aygenli, Fatih"},{"first_name":"Lukas A.","last_name":"Huschet","full_name":"Huschet, Lukas A."},{"full_name":"Popp, Tanja","last_name":"Popp","first_name":"Tanja"},{"last_name":"Ribeiro","first_name":"Andrea","full_name":"Ribeiro, Andrea"},{"id":"db547c8c-329f-11ee-a353-cde802618f9e","first_name":"Darina","last_name":"Barkhatova","orcid":"0000-0002-0062-2817","full_name":"Barkhatova, Darina"},{"last_name":"Jouffe","first_name":"Céline","full_name":"Jouffe, Céline"},{"full_name":"Trozzo, Ricardo","last_name":"Trozzo","first_name":"Ricardo"},{"full_name":"Menet, Jerome S.","first_name":"Jerome S.","last_name":"Menet"},{"last_name":"Rad","first_name":"Roland","full_name":"Rad, Roland"},{"full_name":"Dyar, Kenneth A.","first_name":"Kenneth A.","last_name":"Dyar"},{"first_name":"Maciej","last_name":"Lech","full_name":"Lech, Maciej"},{"full_name":"Straub, Tobias","last_name":"Straub","first_name":"Tobias"},{"full_name":"Michael, Alicia","orcid":"0000-0002-6080-839X","last_name":"Michael","id":"6437c950-2a03-11ee-914d-d6476dd7b75c","first_name":"Alicia"},{"last_name":"Robles","first_name":"Maria S.","full_name":"Robles, Maria S."}],"citation":{"mla":"Aygenli, Fatih, et al. “CLOCK/BMAL1 Interactome Uncovers Homeodomain Factors as Tissue Regulators.” <i>Nature Cell Biology</i>, Springer Nature, 2026, doi:<a href=\"https://doi.org/10.1038/s41556-026-02041-4\">10.1038/s41556-026-02041-4</a>.","ieee":"F. Aygenli <i>et al.</i>, “CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators,” <i>Nature Cell Biology</i>. Springer Nature, 2026.","ama":"Aygenli F, Huschet LA, Popp T, et al. CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators. <i>Nature Cell Biology</i>. 2026. doi:<a href=\"https://doi.org/10.1038/s41556-026-02041-4\">10.1038/s41556-026-02041-4</a>","ista":"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.","apa":"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. <i>Nature Cell Biology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41556-026-02041-4\">https://doi.org/10.1038/s41556-026-02041-4</a>","short":"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).","chicago":"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.” <i>Nature Cell Biology</i>. Springer Nature, 2026. <a href=\"https://doi.org/10.1038/s41556-026-02041-4\">https://doi.org/10.1038/s41556-026-02041-4</a>."},"dataavailabilitystatement":"Proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE64 partner repository with the dataset identifiers PXD062751 and PXD077567. RNA-seq data are available in the European Nucleotide Archive (ENA) under accession no. PRJEB93884, and ChIP–seq data at the Gene Expression Omnibus (GEO) under accession no. GSE302237. AlphaFold 3 interaction prediction parameters can be provided during the revision process on editorial and/or review request. Source data are provided with this paper.","department":[{"_id":"GradSch"},{"_id":"AlMi"}],"day":"06","month":"08","researchdata_availability":"yes","date_published":"2026-08-06T00:00:00Z","status":"public","article_processing_charge":"Yes (via OA deal)","oa_version":"Published Version"}]