The Human Prolactin Receptor Gene Structure and Alternative Promoter Utilization: The Generic Promoter hPII and a Novel Human Promoter hPN

Abstract

The 5′-untranslated region of the human prolactin receptor (hPRLR) gene contains two alternative first exons, hE13, the human counterpart of the rat and mouse E13, and a novel human type of alternative first exon termed hE1N, also a common non-coding exon 2 and a third exon containing the translation initiation codon. hE13 was localized ∼800 bp 5′ from the hE1N in the genome. The two distinct first exons hE13 and hE1N are expressed in human breast tissue, breast cancer cells, gonads and liver. Overall, the transcript containing hE13 is prevalent in most tissues. The coding region of the gene comprises eight exons (exons 3–10), in which exon 10 encodes most of the intracellular domain. hE13 and hE1N are transcribed from alternative promoters hPIII and hPN, respectively. The hPIII, containing identical Sp1 and C/EBP elements as in the rodent promoters, shares 81% similarity in the region −480/−106 to both the rat and mouse. The novel promoter hPN contains putative binding sites for ETS-family proteins and a half-site for nuclear receptors. Therefore, both promoters likely utilize distinct mechanisms in controlling the hPRLR gene transcription. The different promoter utilization of the hPRLR gene in diverse tissues may confer differential prolactin response through activation of different promoters.