Circadian enhancer profiling in diet-induced obese mice reveals a critical time window for lipid-lowering therapies

The 24-hour rhythms in physiology and behavior are controlled by endogenous cellular clocks found in all cells and tissue of the body. At the molecular level, these clocks are based on interlocked transcriptional-translational feedback loops comprised of a set of clock genes and proteins (1). While the nature of the core clockwork is conserved across all tissues, the output from these clocks is highly cell type-specific and believed to be specified by tissue-specific cistromes including enhancer sites, where transcription factor binding leads to regulation of gene transcription over large genomic distances. Under normal metabolic conditions, 5–10% of active transcripts oscillate in a circadian fashion within a tissue. In the mouse, up to 50% of genes are clock-controlled in at least on tissue of the body (2).