Mechanisms of transcriptional activation of the stimulator of interferon genes by transcription factors CREB and c-Myc.
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.
Department of Laboratory Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.|Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.|Department of Pediatrics, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210006, China.
Yan-Yan
YY
Wang
Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
Rui
R
Jin
Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
Guo-Ping
GP
Zhou
Department of Laboratory Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
Hua-Guo
HG
Xu
D047369:Chromatin Immunoprecipitation; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D024363:Transcription Initiation Site; D015533:Transcriptional Activation; D000099197:STING Protein
D017362:Cyclic AMP Response Element-Binding Protein; D008565:Membrane Proteins; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; C115163:CREB1 protein, human; C489427:MYC protein, human; C532857:STING1 protein, human; D000099197:STING Protein
CREB; c-Myc; promoter; stimulator of interferon genes