Heterodimers of the transcription factors BMAL1 and CLOCK upregulate the expression of many target genes. Of these, the protein products of the Period (Per) and Cryptochrome (Cry) genes provide a feedback mechanism to inhibit the transcriptional activity of CLOCK-BMAL1. The activity of PER-CRY dimers is regulated at a posttranscriptional level via phosphorylation by kinases, including casein kinase 1ε (CKI). Other gene targets of CLOCK-BMAL1 include the nuclear receptors retinoid-related orphan receptor α (RORα) and REV-ERBα, which, respectively, promote and inhibit the transcription of Bmal1. In addition to these core components of the genetic clock, CLOCK-BMAL1 regulates the expression of a number of downstream targets that are referred to as clock-controlled genes (CCGs) (13, 14) P, phosphorylation.