The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the β-catenin/TCF target gene matrilysin

Christopher M. Spring, Kevin F. Kelly, Ita O'Kelly, Monica Graham, Howard C. Crawford, Juliet M. Daniel

Research output: Contribution to journalArticle

96 Citations (Scopus)

Abstract

The POZ-zinc finger transcription factor Kaiso was first identified as a specific binding partner for the Armadillo catenin and cell adhesion cofactor, p120ctn. Kaiso is a unique POZ protein with bi-modal DNA-binding properties; it associates with a sequence-specific DNA consensus Kaiso binding site (KBS) or methylated CpG dinucleotides, and regulates transcription of artificial promoters containing either site. Interestingly, the promoter of the Wnt/β-catenin/TCF target gene matrilysin possesses two conserved copies of the KBS, which suggested that Kaiso might regulate matrilysin expression. In this study, we demonstrate using chromatin immunoprecipitation analysis that Kaiso associates with the matrilysin promoter in vivo. Minimal promoter assays further confirmed that Kaiso specifically repressed transcription of the matrilysin promoter; mutation of the KBS element or RNAi-mediated depletion of Kaiso abrogated this effect. More importantly, Kaiso blocked β-catenin-mediated activation of the matrilysin promoter. Consistent with our previous findings, both Kaiso-DNA binding and Kaiso-mediated transcriptional repression of the matrilysin promoter were inhibited by overexpression of wild-type p120ctn, but not by a p120ctn mutant exhibiting impaired nuclear import. Collectively, our data establish Kaiso as a sequence-specific transcriptional repressor of the matrilysin promoter, and suggest that p120ctn and β-catenin act in a synergistic manner, via distinct mechanisms, to activate matrilysin expression.

Original languageEnglish (US)
Pages (from-to)253-265
Number of pages13
JournalExperimental Cell Research
Volume305
Issue number2
DOIs
StatePublished - May 1 2005
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 7
Catenins
Genes
Binding Sites
Armadillos
Cell Nucleus Active Transport
delta catenin
Chromatin Immunoprecipitation
DNA
Zinc Fingers
RNA Interference
Cell Adhesion
Transcription Factors
Mutation

Keywords

  • β-catenin
  • Kaiso
  • matrilysin
  • p120
  • POZ-ZF
  • Transcriptional repression

ASJC Scopus subject areas

  • Cell Biology

Cite this

The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the β-catenin/TCF target gene matrilysin. / Spring, Christopher M.; Kelly, Kevin F.; O'Kelly, Ita; Graham, Monica; Crawford, Howard C.; Daniel, Juliet M.

In: Experimental Cell Research, Vol. 305, No. 2, 01.05.2005, p. 253-265.

Research output: Contribution to journalArticle

Spring, Christopher M. ; Kelly, Kevin F. ; O'Kelly, Ita ; Graham, Monica ; Crawford, Howard C. ; Daniel, Juliet M. / The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the β-catenin/TCF target gene matrilysin. In: Experimental Cell Research. 2005 ; Vol. 305, No. 2. pp. 253-265.
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