CNR1 Promoter Regulation

The transcriptional regulation of the cannabinoid receptor 1 (the CB1R protein & the CNR1 gene) by promoter/enhancer elements and transcription factors is an area of cannabinoid research that has historically been understudied. To map the promoter region of the human CNR1 gene, a 997 base pair fragment from the sequence upstream of the CNR1 gene was cloned into a secreted luciferase reporter vector and a series of deletion fragments were constructed. The transcriptional activity of these constructs was tested in human cell lines from three tissues: neuronal tissue (SHSY5Y), kidney tissue (HEK293T), and colonic epithelium (HCT116). Through this mapping, we have identified two key regulatory regions within the promoter. Increased levels of cAMP suppressed reporter expression in a cell type-specific manner, and in silico modeling predicts potential cAMP response elements (CRE) within one of the key regulatory sequences. Additionally, the minimal promoter region for CNR1 appears to be located in the second regulatory region identified, and in silico modeling predicts BRE and INR elements within this sequence. These findings begin to unravel the mechanisms by which CNR1 is transcriptionally regulated.