Mechanisms of transcriptional activation of the stimulator of interferon genes by transcription factors CREB and c-Myc

// Yan-Yan Wang 1, 2, 3 , Rui Jin 2 , Guo-Ping Zhou 2 , Hua-Guo Xu 1 1 Department of Laboratory Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China 2 Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China 3 Department of Pediatrics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210006, China Correspondence to: Hua-Guo Xu, email: huaguoxu@njmu.edu.cn Guo-Ping Zhou, email: gpzhou2003@126.com Keywords: stimulator of interferon genes, promoter, CREB, c-Myc Received: September 09, 2016     Accepted: October 14, 2016     Published: November 07, 2016 ABSTRACT Stimulator of interferon genes (STING) plays an important role in host defense, autoimmune disease, osteoclast differentiation and anti-tumor response. Although many downstream targets have been studied in depth, the regulation of STING gene expression remains largely unknown. Here we demonstrate that transcription factors CREB and c-Myc maintain the transcriptional activity of STING. By 5′-rapid amplification of cDNA ends analysis, we identified the transcriptional start site (TSS) of STING. We illustrated that the region -124/+1 relative to TSS was sufficient for full promoter activity by a series of 5′ deletion promoter constructs. Transcriptional activity of the STING minimal promoter was dependent on CREB and c-Myc binding motifs and was abolished after mutation of these two DNA elements. Chromatin immunoprecipitation assays demonstrated that transcription factors CREB and c-Myc bind to STING promoter in vivo. Overexpression of CREB and c-Myc increased the STING promoter activity. Meanwhile, knocking-down of CREB and c-Myc by a small interfering RNA (siRNA) strategy markedly reduced endogenous STING expression. In summary, these results demonstrated that transcription factors CREB and c-Myc are involved in the regulation of STING transcription.