Oncotarget

Research Papers:

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

Yan-Yan Wang, Rui Jin, Guo-Ping Zhou and Hua-Guo Xu _

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Oncotarget. 2016; 7:85049-85057. https://doi.org/10.18632/oncotarget.13183

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Abstract

Yan-Yan Wang1,2,3, Rui Jin2, Guo-Ping Zhou2, Hua-Guo Xu1

1Department of Laboratory Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China

2Department of Pediatrics, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China

3Department 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.


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