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Aygenli, F.* ; Huschet, L.A.* ; Popp, T.* ; Ribeiro, A.* ; Barkhatova, D.* ; Jouffe, C. ; Trozzo, R.* ; Menet, J.S.* ; Rad, R.* ; Dyar, K.A. ; Lech, M.* ; Straub, T.* ; Michael, A.K.* ; Robles, M.S.*

CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators.

Nat. Cell Biol., DOI: 10.1038/s41556-026-02041-4 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Circadian Gene-expression; Transcription Factor; Clock; Protein; Prox1; Phosphorylation; Identification; Proteomics; Modulator; Rhythms
ISSN (print) / ISBN 1465-7392
e-ISSN 1476-4679
Journal Nature Cell Biology
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Cancer (IDC)
Grants EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
Deutsche Forschungsgemeinschaft (German Research Foundation)
U.S. Department of Health & Human Services | NIH | National Center for Research Resources (NCRR)
Ludwig-Maximilians-Universitt Mnchen (Ludwig Maximilians University Munich)