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.
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DOI：
10.1016/j.molimm.2012.06.005
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发表时间：
2012-10
影响因子：
3.6
通讯作者：
Agrawal A
中科院分区：
文献类型：
--
作者：
Voleti B;Hammond DJ Jr;Thirumalai A;Agrawal A
c反应蛋白（CRP）是先天免疫系统的一种血浆蛋白，由肝细胞产生。CRP启动子上的一个关键调控区（- 42至- 57）包含il -6激活的转录因子C/EBPβ的结合位点。il -1β激活的转录因子NF-κB与附近的κB位点结合（−63 ~−74）。κB位点与一个八聚体基序（- 59 ~ - 66）重叠，该八聚体基序是组成型活性转录因子Oct-1的结合位点。已知Oct-1既作为转录抑制因子又作为激活因子，这取决于启动子的背景。此外，Oct-1可以通过直接与启动子结合或与其他与启动子结合的转录因子相互作用来调节基因表达。本研究旨在探讨Oct-1在调节CRP表达中的作用。在荧光素酶转激活实验中，过表达的Oct-1抑制了Hep3B细胞中（IL-6+IL-1β）诱导的CRP表达。从启动子中删除Oct-1位点会显著降低细胞因子反应，因为删除Oct-1位点会改变κB位点。令人惊讶的是，过表达的Oct-1通过缺乏Oct-1位点的启动子抑制了残留的（IL-6+IL-1β）诱导的CRP表达。同样，Oct-1位点的缺失减少了C/EBPβ过度表达对CRP表达的诱导，而过表达的Oct-1通过缺乏Oct-1位点的启动子抑制了C/EBPβ诱导的CRP表达。我们得出结论，Oct-1作为CRP表达的转录抑制因子，它通过占据其在启动子上的同源位点以及通过其他转录因子，以一种尚未确定的机制发挥作用。
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.
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影响因子：
7.8
作者：
Grimm AA;Brace CS;Wang T;Stormo GD;Imai S
通讯作者：
Imai S
DOI：
10.1073/pnas.86.21.8202
发表时间：
1989-11-01
影响因子：
11.1
作者：
POLI, V;CORTESE, R
通讯作者：
CORTESE, R
影响因子：
8.7
作者：
Ghosh S;Hayden MS
通讯作者：
Hayden MS
影响因子：
4.4
作者：
Cha-Molstad, H;Agrawal, A;Kushner, I
通讯作者：
Kushner, I
影响因子：
13.5
作者：
CASTELL, JV;GOMEZLECHON, MJ;HEINRICH, PC
通讯作者：
HEINRICH, PC