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.
Highlights
Stimulator of interferon genes (STING) [1,2,3,4], is a multispanning transmembrane protein that was originally identified as a growth inhibitor that mediates anti-MHC class II antibody-induced death in B lymphoma cells [5]
We demonstrate that transcription factors CREB and c-Myc maintain the transcriptional activity of STING
Recent evidence suggested that STING gets involved in STINGTBK1-IRF3 signaling pathway by three distinct cytosolic nucleic acid–sensing pathways, RNA sensing through RLRs, DNA detection by DDX41 and the ALR IFI16, and the sensing of bacterial cyclic dinucleotides, such as c-di-GMP (c[G(3’ -5’)pG(3’ -5’)p] or cyclic di-AMP or cyclic GAMP [2, 7,8,9]
Summary
Stimulator of interferon genes (STING) ( known as MITA, MPYS, ERIS and TMEM173) [1,2,3,4], is a multispanning transmembrane protein that was originally identified as a growth inhibitor that mediates anti-MHC class II antibody-induced death in B lymphoma cells [5]. Chromatin immunoprecipitation assays demonstrated that transcription factors CREB and c-Myc bind to STING promoter in vivo. We identified the minimal promoter of STING is located within the region -124/+1 bp relative to the transcription start site (TSS) and demonstrated that transcription factors CREB and c-Myc maintain the transcriptional activity of STING.
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