Beta-catenin binds to the downstream region and regulates the expression C-reactive protein gene.
C-Reactive protein (CRP) is a major acute-phase response protein, which is activated by various cytokines. We investigated the mechanism of TNF-alpha-induced CRP expression and found that the p50 subunit of NF-kappaB 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 beta-catenin enhanced the expression of a CRP mRNA in concert with p50 subunit. Protein-protein interaction between p50 and beta-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 beta-catenin in the downstream of CRP gene by 3C and confirmed TNF-alpha-induced association of beta-catenin and p50 by chromatin immunoprecipitation and co-immunoprecipitation assays. Our findings provide evidence that transcription of the CRP gene depends upon p50 and beta-catenin proteins, which is accompanied by close proximity between promoter and the downstream region of CRP gene.
Choi
Yong Seok
YS
Department of Molecular Biology, BK21 Graduate Program for RNA Biology, Institute of Nanosensor and Biotechnology, Dankook University, Seoul 140-714, Republic of Korea.
Hur
Jung
J
Jeong
Sunjoo
S
D001665:Binding Sites; D002097:C-Reactive Protein / Q000096:biosynthesis / Q000235:genetics*; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D006801:Humans; D052002:NF-kappa B p50 Subunit / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D050436:Regulatory Elements, Transcriptional; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism*
D052002:NF-kappa B p50 Subunit; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin; D002097:C-Reactive Protein
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