کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2830943 | 1570730 | 2012 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Oct-1 acts as a transcriptional repressor on the C-reactive protein promoter Oct-1 acts as a transcriptional repressor on the C-reactive protein promoter](/preview/png/2830943.png)
C-reactive protein (CRP), a plasma protein of the innate immune system, is produced by hepatocytes. A critical regulatory region (−42 to −57) on the CRP promoter contains binding site for the IL-6-activated transcription factor C/EBPβ. The IL-1β-activated transcription factor NF-κB binds to a κB site located nearby (−63 to −74). The κB site overlaps an octamer motif (−59 to −66) which is the binding site for the constitutively active transcription factor Oct-1. Oct-1 is known to function both as a transcriptional repressor and as an activator depending upon the promoter context. Also, Oct-1 can regulate gene expression either by binding directly to the promoter or by interacting with other transcription factors bound to the promoter. The aim of this study was to investigate the functions of Oct-1 in regulating CRP expression. In luciferase transactivation assays, overexpressed Oct-1 inhibited (IL-6 + IL-1β)-induced CRP expression in Hep3B cells. Deletion of the Oct-1 site from the promoter drastically reduced the cytokine response because the κB site was altered as a consequence of deleting the Oct-1 site. Surprisingly, overexpressed Oct-1 inhibited the residual (IL-6 + IL-1β)-induced CRP expression through the promoter lacking the Oct-1 site. Similarly, deletion of the Oct-1 site reduced the induction of CRP expression in response to overexpressed C/EBPβ, and overexpressed Oct-1 inhibited C/EBPβ-induced CRP expression through the promoter lacking the Oct-1 site. We conclude that Oct-1 acts as a transcriptional repressor of CRP expression and it does so by occupying its cognate site on the promoter and also via other transcription factors by an as yet undefined mechanism.
► On the CRP promoter, Oct-1 acts as a transcriptional repressor.
► To repress CRP expression, Oct-1 uses two mechanisms.
► One mechanism involves binding of Oct-1 to the CRP promoter.
► The other mechanism involves interactions of Oct-1 with other transcription factors bound to the CRP promoter.
Journal: Molecular Immunology - Volume 52, Issues 3–4, October–December 2012, Pages 242–248