Cloning of the rat β-catenin gene (Ctnnb1) promoter and its functional analysis compared with the Catnb and CTNNB1 promoters

Qingjie Li, Wan Mohaiza Dashwood, Xiaoying Zhong, Mohamed Al-Fageeh, Roderick H. Dashwood

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Considerable recent interest has focused on the stabilization and accumulation of β-catenin protein in human and animal tumors and the corresponding activation of downstream β-catenin/TCF/LEF target genes. However, there is only sparse information on the regulation of β-catenin expression at the transcriptional level and its possible involvement in physiological and pathophysiological processes. We report here the cloning and characterization of a 3.6-kb promoter fragment from the rat β-catenin gene, Ctnnb1, and its comparison with corresponding promoters from the mouse and human genes, Catnb and CTNNB1. Several AP1 binding sites were confirmed in the promoters of all three species using mobility shift and reporter assays, and one putative TCF/LEF site also was observed in the promoter of CTNNB1. Subsequently, protein/DNA array analyses identified numerous other transcription factors through their high-affinity binding to the Ctnnb1 promoter, including E2F1, NFκB, MEF1, Pax5, ISRE2, Smad3/4, GATA, and ZIC. The strong binding of E2F1 and NFκB is especially noteworthy, because the former transcription factor is regulated by cyclin D1, a downstream target of β-catenin/TCF/LEF signaling, whereas the latter transcription factor has been implicated in "cross talk" between the Wnt and the NFκB signaling pathways. These results are discussed in terms of their implications for human cancer development and specifically the various tumors in which β-catenin mRNA is overexpressed, as well as for embryonic development, when reversible changes in β-catenin expression occur in response to secreted Wnt ligands. The findings reported here should provide important avenues for further research focused on the regulation of Ctnnb1 activity, including the ability of β-catenin/Tcf downstream targets to modulate β-catenin expression at the transcriptional level.

Original languageEnglish (US)
Pages (from-to)231-242
Number of pages12
JournalGenomics
Volume83
Issue number2
DOIs
StatePublished - Feb 2004
Externally publishedYes

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Catenins
Organism Cloning
Genes
Transcription Factors
Physiological Phenomena
Neoplasms
Protein Array Analysis
Wnt Signaling Pathway
Aptitude
Cyclin D1
Human Development
Electrophoretic Mobility Shift Assay
Oligonucleotide Array Sequence Analysis
Embryonic Development
Binding Sites
Ligands
Messenger RNA

ASJC Scopus subject areas

  • Genetics

Cite this

Cloning of the rat β-catenin gene (Ctnnb1) promoter and its functional analysis compared with the Catnb and CTNNB1 promoters. / Li, Qingjie; Dashwood, Wan Mohaiza; Zhong, Xiaoying; Al-Fageeh, Mohamed; Dashwood, Roderick H.

In: Genomics, Vol. 83, No. 2, 02.2004, p. 231-242.

Research output: Contribution to journalArticle

Li, Qingjie ; Dashwood, Wan Mohaiza ; Zhong, Xiaoying ; Al-Fageeh, Mohamed ; Dashwood, Roderick H. / Cloning of the rat β-catenin gene (Ctnnb1) promoter and its functional analysis compared with the Catnb and CTNNB1 promoters. In: Genomics. 2004 ; Vol. 83, No. 2. pp. 231-242.
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