Kaiso Protein in the Regulation of Brain and Behavior

Abstract

Kaiso is a bimodal transcriptional repressor. It binds methylated CpG islands or the sequence- specific consensus in the DNA molecule with the Kaiso zinc-finger domain and recruits repressive protein complexes to these DNA fragments by the interaction of the BTB/POZ domain with the complex of NCoR1 corepressor and histone deacetylase, thereby performing transcription repression. Kaiso is involved in epigenetic regulation of transcription. Moreover, the complex Kaiso and catenin p120ctn modulates the transcription of the Wnt-target genes. The review discusses the role of Kaiso in the central nervous system. Kaiso molecules are abundant in the brain. MRI study did not show any alterations in the whole brain, hippocampus and striatum in Kaiso null mice. However, in Kaiso deficient mice the lateral ventricles were three-fold smaller compared with wild-type control. Kaiso deficiency increased the locomotor and exploratory activities as well as the prepuls inhibition of acoustic startle reflex without any adverse effect on anxiety-related behavior, learning and memory. At the same time, Kaiso deficiency produces a marked antidepressant-like effect. Thus, Kaiso involved in the mechanism of locomotion and depressive-like behavior. Kaiso inhibitors are expected to be promising atypical antidepressant drugs.

Keywords: DNA methylation; Kaiso; Wnt signaling; Zbtb33; behavior; brain..