Kaiso is a novel member of the BTB/POZ (Broad complex, Tramtrak, Bric a
brac,/Pox virus and zinc finger) zinc finger family of transcriptional regulators that have
many roles in development and tumorigenesis. Kaiso was first identified as a binding
partner for p 120ctn, an Armadillo catenin with roles in cell adhesion and stabilization of
cadherins at the cell membrane. Kaiso is both an activator and repressor of gene
transcription and interacts with two distinct types of DNA sequence; a consensus Kaiso
binding site (KBS) TCCTGCNA and methylated CpG dinucleotide pairs (i.e. CpGCpG).
Thus far p120's nuclear role is to inhibit Kaiso-mediated regulation of its target genes.
Some of the Kaiso target genes identified to date include, matrilysin, rapsyn, and MTA2.
The Kaiso homologue in Xenopus laevis (frog) has also been shown to regulate the cell
cycle regulator CCND 1. Sequence analysis of the human CCND1 promoter revealed
several potential Kaiso binding elements including both KBS and methylatable CpGs. My research demonstrated that Kaiso binds to the CCND1 promoter in vitro and
in vivo to both KBS-specific and CpG-specific regions. Furthermore, I determined that
Kaiso may act as either a repressor or activator of the human CCND 1 gene depending on
the cellular environment. Altogether these data support my hypothesis that Kaiso is a
regulator of the CCND1 gene. Future studies looking at the significance of KBS versus
CpG-binding on Kaiso's mechanism of regulation are required to determine the
significance of this regulation. Furthermore, studies examining the cell cycle-dependent
changes in Kaiso levels may reveal how alterations in Kaiso expression affect Kaiso
target genes including CCND1. / Thesis / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/21672 |
| Date | 08 1900 |
| Creators | Anstey, Michelle |
| Contributors | Daniel, Juliet, Biology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
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