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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.<\/jats:p>","DOI":"10.1038\/s41556-026-02041-4","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T09:01:53Z","timestamp":1786006913000},"page":"1890-1900","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CLOCK\/BMAL1 interactome uncovers homeodomain factors as tissue regulators"],"prefix":"10.1038","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8749-2324","authenticated-orcid":false,"given":"Fatih","family":"Aygenli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas A.","family":"Huschet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Popp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darina","family":"Barkhatova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7176-4724","authenticated-orcid":false,"given":"C\u00e9line","family":"Jouffe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5889-994X","authenticated-orcid":false,"given":"Riccardo","family":"Trozzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome S.","family":"Menet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6849-9659","authenticated-orcid":false,"given":"Roland","family":"Rad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9010-8757","authenticated-orcid":false,"given":"Kenneth A.","family":"Dyar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4293-2733","authenticated-orcid":false,"given":"Maciej","family":"Lech","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Straub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia K.","family":"Michael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9149-8761","authenticated-orcid":false,"given":"Maria S.","family":"Robles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"2041_CR1","doi-asserted-by":"publisher","unstructured":"Trip, D. 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