期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 277, 期 45, 页码 42438-42446出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M207363200
关键词
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资金
- NIGMS NIH HHS [GM59473] Funding Source: Medline
The ILRE (interleukin response element) contained within the promoter of the interleukin-6 (IL-6) gene is defined as the site recognized by the p65 NF-kappaB transcriptional activator and is crucial for activation of the IL-6 gene. The region of the promoter containing the ILRE is complex containing a CCAAT enhancer-binding protein (C/EBP) site immediately upstream of the ILRE, which is required for optimal activation of the IL-6 gene. Additionally, the ILRE overlaps a site that is recognized by the mammalian transcriptional repressor RBP (CBF-1), and RBP binding within the ILRE region represses activated IL-6 expression. In this study, the complexity of this region is further revealed by the identification of a second nested C/EBP site, which overlaps that of RBP and therefore also the ILRE. Optimal activation requires both the upstream and newly identified C/EBP sites in conjunction with the p65 NF-kappaB binding site. We previously reported that RBP represses IL-6 activation but does not target p65. We extend these analyses here to show that RBP binding does not occlude p65 from binding but instead directly overlaps the newly identified downstream C/EBP site, thereby impeding p65-C/ EBP-mediated co-activation. This result suggests a role for RBP in the repression of other genes containing a C/EBP site that exhibits sequence overlap with the RBP site.
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