Structural Organization and Transcriptional Regulation of the Human beta_1-Adrenergic Receptor Gene

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To investigate the effects of antidepressant treatment on the beta_1-adrenergic receptor(AR) at transcriptional levels, the delineation of the structural organization of the human beta_1-AR gene was attempted. A genomic clone was obtained from human placental genomic library through repeated screenings using the 1.3-kb(kilobase) Smal fragment human beta_1-AR cDNA(complementary DNA) probe. Restriction endonuclease fragments of interest were subcloned into pUC18 and sequenced by the dideoxy chain-termination method.The proximal promoter region (-1300 through -50 relative to the adenosine of the first methionine codon) lacks TATA box, is rich in G + C content, and has multiple putative binding sites for transcriptional factor Sp1 and AP-2. Thus, the proximal promoter region has features of "house- keeping" genes.The distal promoter region (-2300 through -1300) has representative TATA box and CAAT box consequences, typical thyroid, estrogen, glucorticoid, cAMP responsive el'ements, and binding sites for transcriptional factor AP-1, GATA-1,2.3, which indicate multiple regulatory mechanisms involved in the beta_1-AR gene expression in vivo. Moreover, there is present in the human genome a long [1032-bp(base pair)] open reading frame which ends only 112-bp 5' to the initiator methionine of the receptor, and which encodes a putative protein of the molecular weight of - 38000.