Transcription factor organic cation transporter 1 (OCT-1) affects the expression of porcine Klotho ( KL ) gene

Klotho (KL), originally discovered as an aging suppressor, was a membrane protein that shared sequence similarity with the β-glucosidase enzymes. Recent reports showed Klotho might have a role in adipocyte maturation and systemic glucose metabolism. However, little is known about the transcription factors involved in regulating the expression of porcine KL gene. Deletion fragment analysis identified KL-D2 (-418 bp to -3 bp) as the porcine KL core promoter. MARC0022311 in KL intron 1 appeared a polymorphism (A or G) in Landrace × DIV pigs, and relative luciferase activity of pGL3-D2-G was significantly higher than pGL3-D2-A . This was possibly the result of a change in KL binding ability with transcription factor organic cation transporter 1 (OCT-1), which was confirmed using electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP). Moreover, OCT-1 regulated endogenous KL expression by RNA interference. Our study indicates SNP MARC0022311 affects porcine KL expression by regulating its promoter activity via OCT-1.