The transcriptional regulation of the human β1-adrenergic receptor gene by stress-related transcription molecules

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We characterized the transcription factors involved in the regulation of the human β1-adrenergic receptor (β1-AR) gene expression and studied effects of stress-related transcription molecules, such as glucocorticoid receptor(GR) and heat shock factors, on the transcription of the β1-AR gene in human neuroblastoma SY5Y ceils. Deletional and mutational analyses of the β1-AR gene promoter-luciferase reporter gene constructs revealed that the trimeric transcription factor NF-Y binding site, located in -369/-365 relative to the translation start codon, has a pivotal role in the regulation of the β 1-AR gene expression. In addition, we found one potential binding site for CREB (-353/-346) and two sites for AP-2 (-345/-337 and -332/-324) near the NF-Y binding site. By introducing mutations into either of the two AP-2 sites, the β1-AR gene expression was moderately reduced. In contrast, CREB binding site mutation was less effective in the reduction of the β1-AR gene expression. These results indicate that NF-Y regulates the β1-AR gene expression by recruiting AP-2. Treatment with glucocorticoid (GC) inhibited the β1-AR gene expression in SY5Y cells. Assuming that GR Interacts with NF-Y through the protein-protein interaction, GC-mediated inhibition of the β1-AR gene expression can occur through the sequestration of NF-Y by GR from the β1-AR gene promoter.