Anti-clustering of circadian gene expression in mouse liver genome

Circadian regulatory system is an evolutionarily ancient biological system. Its prevalence in life kingdoms suggests it has fundamental role in life processes. Although genomic scale of circadian gene expression has been found in various species from cyanobacteria to mammalians, transcriptional patterns and mechanisms of global circadian gene regulation have not yet been revealed. Using high resolution temporal profiling of mouse circadian gene expression, we show that contrary with previously demonstrated clustering tendency of functionally related genes in mammalian genomes, circadian regulated genes display anti-clustering propensity in mouse liver. This unique property does not conform to the notion of domain-wide coordinated gene regulation dictated by acetyl modifications, which is recently identified as a hallmark of circadian regulation. These results suggest that global circadian regulation in mouse liver might involve other structural chromosome interactions irrelevant with clustering regulation.