Nucleic Acids Research Advance Access published online on August 17, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm547
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Molecular Biology |
ß-Catenin binds to the downstream region and regulates the expression C-reactive protein gene
Department of Molecular Biology, BK21 Graduate Program for RNA Biology, Institute of Nanosensor and Biotechnology, Dankook University, Seoul 140-714, Republic of Korea
*To whom correspondence should be addressed. Tel: +82 2 709 2819; Fax: +82 2 793 0176; Email: sjsj{at}dankook.ac.kr
Received February 18, 2007. Revised June 19, 2007. Accepted July 9, 2007.
C-Reactive protein (CRP) is a major acute-phase response protein, which is activated by various cytokines. We investigated the mechanism of TNF-
-induced CRP expression and found that the p50 subunit of NF-
B was responsible for the transcriptional activation of CRP. Since the p50 protein acts as a positive regulator of CRP expression without an inherent transactivation domain, we looked for an interaction partner that could provide p50 with such a domain. We found that ß-catenin enhanced the expression of a CRP mRNA in concert with p50 subunit. Protein–protein interaction between p50 and ß-catenin was important for CRP expression and their interactions to CRP promoter were induced after TNF-a treatment. Since gene expression depends upon the proximity of promoters and distal regulatory sites, we explored the long-range genomic interaction at the CRP locus by chromosome conformation capture (3C). We identified a binding site for ß-catenin in the downstream of CRP gene by 3C and confirmed TNF-
-induced association of ß-catenin and p50 by chromatin immunoprecipitation and co-immunoprecipitation assays. Our findings provide evidence that transcription of the CRP gene depends upon p50 and ß-catenin proteins, which is accompanied by close proximity between promoter and the downstream region of CRP gene.
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