TY - JOUR
T1 - The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the β-catenin/TCF target gene matrilysin
AU - Spring, Christopher M.
AU - Kelly, Kevin F.
AU - O'Kelly, Ita
AU - Graham, Monica
AU - Crawford, Howard C.
AU - Daniel, Juliet M.
N1 - Funding Information:
The authors wish to thank Dr. A.B. Reynolds for supplying us with needed reagents and p120 ctn -specific antibodies. We also wish to thank Abena Otchere for experimental and editorial assistance, and Drs. J.R. Jacobs and J. Lee for technical advice. KFK is a recipient of an NSERC PGSD2 scholarship. This work was supported by a CIHR grant (MOP-42405) and Ontario PREA (00/6-950) to J.M.D. and H.C.C. was supported by NIH RO1 CA-10012601.
PY - 2005/5/1
Y1 - 2005/5/1
N2 - 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.
AB - 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.
KW - Kaiso
KW - POZ-ZF
KW - Transcriptional repression
KW - matrilysin
KW - p120
KW - β-catenin
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UR - http://www.scopus.com/inward/citedby.url?scp=16344366009&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2005.01.007
DO - 10.1016/j.yexcr.2005.01.007
M3 - Article
C2 - 15817151
AN - SCOPUS:16344366009
SN - 0014-4827
VL - 305
SP - 253
EP - 265
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 2
ER -