Chromatin conformation capture (4C-seq) from mouse liver
The circadian clock system coordinates metabolic, physiological, and behavioral functions across a 24-hour cycle, crucial for adapting to environmental changes. Disruptions in circadian rhythms contribute to major metabolic pathologies like obesity and Type 2 diabetes. Understanding the regulatory mechanisms governing circadian control is vital for identifying therapeutic targets. It is well characterized that chromatin remodeling at distal enhancer elements shapes the genome topology, supporting rhythmic transcriptional cycles; yet the impact of rhythmic chromatin topology and circadian enhancers in disease states is largely unexplored. In his study, we use 4C-seq techniques in mouse liver to explore how the spatial configuration of the genome adapts to diet, rewiring circadian transcription and contributing to dysfunctional metabolism. We describe daily fluctuations in chromatin contacts between distal regulatory elements of metabolic control genes in livers from lean and obese mice and identify specific lipid-responsive regions recruiting the clock molecular machinery. Our findings highlight the intricate coupling of circadian gene expression to a dynamic nuclear environment under high-fat feeding, supporting a temporally regulated program of gene expression and transcriptional adaptation to diet. Overall design: Chromatin conformation capture (4C-seq) from mouse liver was used to asses genomic contacts engaged by regulatory elements from the Dbp, Srepbp1c, Ppara and Pparg2 genes. Mice were fed either a control or a high fat diets and livers were harvested at two circadian time points: ZT6 and ZT18. Two biological replicates were used per condition.