Transcriptional properties of the Kaiso class of transcription factors

Kaiso, Kaiso-Like-1 (KL1), and ZBTB38 comprise a novel class of transcription factors which can bind both methylated and non-methylated DNA sequences. These transcription factors have N-terminal POZ (pox virus and zinc finger) domains, and C-terminal zinc finger domains. Kaiso was identified as binding partner to p120 catenin (p120). p120 is an armadillo domain containing cell adhesion regulator with functions in maintaining cell-cell junctions and also in the nucleus. p120 can translocate to the nucleus and disrupt Kaiso transcriptional properties by binding to Kaiso's zinc finger domains. While evidence shows that the Kaiso family of transcription factors are primarily transcriptional repressors, their mechanism of repression and their gene targets in mammalian systems remains largely unknown.; I have identified Kaiso and KL1 as binding partners to the mammalian mSin3a protein. mSin3a is scaffold protein and core component of a co-repressor complex which recruits chromatin remodeling activity, including histone deacetylase (HDAC) activity, to DNA binding transcription factors. I identified Kaiso as a mSin3a binding partner from a 2-hybrid screen with the mSin3a HDAC interaction domain. Kaiso and mSin3a form a detectable endogenous complex in epithelial cells. Kaiso acts as a repressor in transient reporter assays and is in protein complexes with HDAC activity.; I have demonstrated that Kaiso can regulate expression of the cell adhesion molecule E-cadherin in breast epithelial cells, implying that p120 can regulate E-cadherin transcription through Kaiso. Kaiso is sumoylated, and this sumoylation may regulate Kaiso's sub-cellular localization. This provides an additional mechanism to regulate Kaiso transcription.; I performed global gene expression analysis on HCT 116 cells with knock downs of mSin3, Kaiso, KL1, and p120. Kaiso did not act as a global repressor of gene expression in these cells, but KL1 and Sin3 had large numbers of changes in gene expression. Overlapping set of genes up were up-regulated in cells knocked down with mSin3 and KL1. Interestingly, some of these genes are p53 transcriptional targets. KL1 also associates with mSin3a and p120 in vivo, suggesting that KL1 transcriptional repression may be regulated by these molecules.