title: Beta-catenin binds to the downstream region and regulates the expression C-reactive protein gene.
abstract: 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.
authors: Department of Molecular Biology, BK21 Graduate Program for RNA Biology, Institute of Nanosensor and Biotechnology, Dankook University, Seoul 140-714, Republic of Korea.
authors: Yong Seok
authors: YS
authors: Choi
authors: Jung
authors: J
authors: Hur
authors: Sunjoo
authors: S
authors: Jeong
mesh_terms: 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*
chemical_list: D052002:NF-kappa B p50 Subunit; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin; D002097:C-Reactive Protein
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