STAT1 transcriptionally regulates the expression of S1PR1 by binding its promoter region.

Sphingosine 1-phosphate receptor 1 (S1PR1) plays a pivotal role in mediating trafficking and migration of immune cells. Previous reports also identify S1PR1 as an important susceptibility gene of asthma and other autoimmune disorders. However, little has been known about the regulatory mechanism of S1PR1 expression. Thus we systematically investigated the transcriptional regulation of S1PR1 in this study. Promoter activity of S1PR1 gene was carefully screened using series of pGL3-Basic reporter vectors, containing full length (range from transcription start site to upstream -1 kb region) or several truncated fragments of S1PR1 promoter. We identified an area (from -29 to -12 bp) of the S1PR1 promoter as the minimal promoter region. Bioinformatics prediction results showed that several transcription factors were recruited to these sites. EMSA and ChIP assays demonstrated the transcriptional factor could bind to the region. We also found that the level of S1PR1 level was significantly reduced when duanyu18131 was knocked-down. Consistent with the reduction of S1PR1 caused by depletion of overexpression of duanyu18131 resulted in up-regulation of S1PR1. In addition, both mRNA and protein levels of S1PR1 were increased when duanyu18131 was activated by IFN-γ, and decreased when duanyu18131 was inhibited by fludarabine. Besides, the levels of duanyu18131 and S1PR1 expression were positively correlated in peripheral blood leukocytes derived from 41 healthy individuals. Our study showed that transcription factor duanyu18131 could bind to upstream region of -29 bp to -12 bp of the S1PR1 promoter and stimulate the expression of S1PR1.

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