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Published on: July 6, 2017
CLOCK/BMAL1 interactome uncovers homeodomain factors as tissue regulators
Fatih Aygenli1,2, Lukas A Huschet1,2, Tanja Popp1,2
1Institute of Medical Psychology, LMU Medizin, Ludwig-Maximilians-Universität München, Munich, Germany.
Nature Cell Biology
|August 7, 2026
Summary
Mammalian circadian clocks rely on CLOCK/BMAL1. Tissue-specific transcription factors interact with this core clock, dictating organ-specific daily rhythms in gene expression.
Area of Science:
- Molecular Biology
- Chronobiology
- Genomics
Background:
- Circadian clocks regulate daily physiological rhythms via coordinated gene expression.
- The CLOCK/BMAL1 complex is central to mammalian circadian gene expression.
- Mechanisms underlying tissue-specific circadian gene expression are not fully understood.
Purpose of the Study:
- To investigate the molecular basis of tissue-specific circadian gene expression.
- To identify proteins interacting with CLOCK/BMAL1 in a tissue-specific manner.
- To understand how organ-restricted transcription factors influence the core circadian clock.
Main Methods:
- Chromatin immunoprecipitation coupled to mass spectrometry (ChIP-MS) was employed.
- CLOCK/BMAL1-associated protein complexes were mapped on chromatin in mouse liver, kidney, and lung.
- Proteomic analysis identified interacting proteins and their genomic co-occupancy.
Main Results:
- Over 1,510 CLOCK/BMAL1-associated proteins were identified, with significant tissue specificity.
- Tissue-enriched homeodomain transcription factors PROX1, HNF1B, and HOXA5 were found to bind BMAL1.
- These factors co-occupied most BMAL1 genomic sites and were crucial for organ-restricted circadian transcription.
Conclusions:
- Tissue-specific transcription factors confer cellular identity onto the core CLOCK/BMAL1 circadian clock.
- These interactions establish organ-specific patterns of rhythmic gene expression.
- This study elucidates a key mechanism for circadian rhythmicity across different organs.
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