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Identification of PARP1 as one of the transcription factors binding to the repressor element in the promoter region of COX2

Identification of PARP1 as one of the transcription factors binding to the repressor element in the promoter region of COX2,10.1016/j.abb.2010.09.016,

Identification of PARP1 as one of the transcription factors binding to the repressor element in the promoter region of COX2   (Citations: 1)
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Cyclooxygenase-2 (COX-2) plays important roles in the development of many disease conditions, including pancreatic β-cell dysfunction. Although the processes involved in the transcriptional regulation of COX-2 are well documented, some key elements, especially inhibitory elements, are still unknown. In our previous study, we identified a novel repressor element located in promoter region of mouse COX-2. In this study, we isolated several DNA-binding proteins from NIT-1 cells via DNA affinity chromatography; the most prominent among these proteins was poly (ADP-ribose) polymerase-1 (PARP-1). In this study, gel-supershift assays and chromatin immunoprecipitation assays showed that PARP-1 can bind to the inhibitory element −655/−632 in the promoter region of mouse COX-2 both in vitro and in vivo. Furthermore, overexpression of PARP-1 significantly inhibited promoter activity and decreased COX-2 expression. Conversely, repression of PARP-1 by RNAi upregulated COX-2 expression. These data suggest that PARP-1 plays an important role in the regulation of COX-2 expression via binding to the inhibitory element. Collectively, our findings provide new important information on the transcriptional regulation of COX-2 in pancreatic β-cells.
Journal: Archives of Biochemistry and Biophysics - ARCH BIOCHEM BIOPHYS , vol. 505, no. 1, pp. 123-129, 2011
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