Phosphoenolpyruvate carboxykinases, or PEPCK, are enzymes synthesized in the liver, they are integral in the metabolic pathway gluconeogenesis; which changes pyruvate to glucose. Various transcription factors are involved in controlling the PEPCK mRNA many hormones act as transcription factors by binding with specific DNA sequences in the regulatory region of the gene. These binding sites are called response elements. The glucocorticoid response element (GRE) stimulates transcription when it is bound to a glucocorticoid receptor (GR). A glucocorticoid is a steroid hormone that promotes the transition of amino acids, like pyruvate, to glucose.
             For a cell to respond to a glucocorticoid, a glucocorticoid receptor must exist. The GR has three domains, a ligand-binding domain (GR binds to a steroid hormone), a DNA-binding domain (GR binds to a specific DNA sequence), and an activation domain (GR binds to other proteins and activates transcription.) As the glucocorticoid hormone enters the cytoplasm of a cell it binds to a GR protein (a ligand-binding domain), which in turn changes the conformation of the protein and exposes a nuclear localization signal (NLS). The GR protein, or NLS bearing protein, binds with the alpha and beta importins forming a complex; this protein complex is moved through the nuclear pore into the nucleus where it interacts with Ran-GTP and dissociates. The GR complex then binds to the GRE, located upstream from the TATA box on the DNA. Transcription is activated once the PC forms.
             The PEPCK gene is expressed by a number of actions that occur at the DNA regulatory sequences. The TATA box, which is the most proximal upstream regulatory sequence, is the site of initiation of transcription and is part of the gene's promoter. The area from the TATA box to the site of transcription activation is referred to as the core promoter. The core promoter is the site where the pre-initiation complex (PC)...