Figure 1.

Circadian regulatory factors in cells of the body. Left: Adipose tissue, which is comprised of adipocyte progenitor cells (APCs), endothelial cells (AECs), and immune cells (AICs) contains the same clock regulatory factors important for rhythmicity in other cell types. Right: The PAS-domain containing transcription factors CLOCK and BMAL1 heterodimerize to form a complex that binds to and generally activates target genes harboring E box consensus sites in the promoter. Target genes include the negative regulators of the complex, including the PER and Cry genes, which when rhythmically expressed, directly interact with the CLOCK:BMAL1 heterodimer and block subsequent transactivation of target genes. Rev-erbα and Rev-erbβ can transcriptionally repress BMAL1 expression, while Rorα and Pparα can transcriptionally activate BMAL1. This transcriptional feedback loop regulates the rhythmicity of hundreds of genes involved in metabolism (resulting in rhythmic metabolite production [2] among other rhythmic cellular processes). However, post-transcriptional and post-translational modifications are also highly dynamic throughout the 24-h cycle. These modifications include acetylation and phosphorylation of proteins within the cell [4,5].