| First Author | Tiwari P | Year | 2013 |
| Journal | Biochim Biophys Acta | Volume | 1830 |
| Issue | 6 | Pages | 3650-5 |
| PubMed ID | 23391827 | Mgi Jnum | J:202437 |
| Mgi Id | MGI:5519022 | Doi | 10.1016/j.bbagen.2013.01.024 |
| Citation | Tiwari P, et al. (2013) Prediction and experimental validation of a putative non-consensus binding site for transcription factor STAT3 in serum amyloid A gene promoter. Biochim Biophys Acta 1830(6):3650-5 |
| abstractText | We previously demonstrated that though the human SAA1 gene shows no typical STAT3 response element (STAT3-RE) in its promoter region, STAT3 and the nuclear factor (NF-kappaB) p65 first form a complex following interleukin IL-1 and IL-6 (IL-1+6) stimulation, after which STAT3 interacts with a region downstream of the NF-kappaB RE in the SAA1 promoter. In this study, we employed a computational approach based on indirect read outs of protein-DNA contacts to identify a set of candidates for non-consensus STAT3 transcription factor binding sites (TFBSs). The binding of STAT3 to one of the predicted non-consensus TFBSs was experimentally confirmed through a dual luciferase assay and DNA affinity chromatography. The present study defines a novel STAT3 non-consensus TFBS at nt -75/-66 downstream of the NF-kappaB RE in the SAA1 promoter region that is required for NF-kappaB p65 and STAT3 to activate SAA1 transcription in human HepG2 liver cells. Our analysis builds upon the current understanding of STAT3 function, suggesting a wider array of mechanisms of STAT3 function in inflammatory response, and provides a useful framework for investigating novel TF-target associations with potential therapeutic implications. |
