{"database":"ENA","file_versions":[],"scores":null,"additional":{"omics_type":["Genomics"],"center_name":["Klinikum rechts der Isar, II. Medizinische Klinik"],"full_dataset_link":["https://www.ebi.ac.uk/ena/browser/view/PRJEB93884"],"long_description":["Although the molecular mechanism of the circadian clock is conserved across cells, its transcriptional outputs are highly tissue specific. To experimentally explore how the core CLOCK/BMAL1 heterodimer achieves this specificity, we investigated its protein interaction landscape at the chromatin by employing a method that combines chromatin immunoprecipitation with mass spectrometry-based quantitative proteomics (ChIP–MS). This approach yielded the first two-dimensional (temporal and tissue-specific) interaction map of CLOCK/BMAL1 at the chromatin and revealed a complex organ-dependent landscape of clock-associated protein interactions. Among these we identified three homeodomain containing transcription factors -PROX1, HFN1B and HOXA5- in liver, kidney and lung, respectively. Functional analyses demonstrated that these factors colocalize with CLOCK/BMAL1 at the chromatin physically interacting via their homeodomain and the BMAL1 C-terminal transactivation domain and act as transcriptional repressors. Deletion of these homeodomain factors in organ-derived cell lines led to upregulation of core clock genes and disrupted rhythmic transcription of tissue-specific targets. Our findings uncover a new class of tissue-specific circadian transcriptional repressors and suggest that the molecular clock does not solely impose a universal temporal program but is instead modulated by chromatin-bound cofactors—such as PROX1, HNF1B, and HOXA5—that shape tissue-specific transcriptional outputs"],"repository":["ENA"],"additional_accession":[]},"is_claimable":false,"name":"","description":"The CLOCK/BMAL1 protein interaction landscape at the chromatin reveals homeodomain transcription factors as modulators of tissue-specific circadian transcription","dates":{"last_updated":"2025-07-16","first_public":"2025-07-16"},"accession":"PRJEB93884","cross_references":{}}