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Biology subjects

Lobanova, Y.

Publications and source records attributed to Lobanova, Y..

2 recordsLinked to original sources

Kaiso regulates DNA methylation homeostasis

Gain and loss of DNA methylation in cells is a dynamic process that tends to achieve an equilibrium. Many factors are involved in maintaining the balance between DNA methylation and demethylation. Previously, it was shown that methyl-DNA protein Kaiso may attract NcoR, SMRT repressive complexes affecting histone modifications. On the other hand, the deficiency of Kaiso resulted in slightly reduced methylation of ICR in H19/Igf2 locus and Oct4 promoter in mouse embryonic fibroblasts. However, nothing is known whether Kaiso may attract DNA methyltransferase to influence DNA methylation level. The main idea of this work is that Kaiso may lead to DNA hypermethylation attracting de novo DNA methyltransferases. We demonstrated that Kaiso regulates TRIM25 promoter methylation. It can form a complex with DNMT3b. BTB/POZ domain of Kaiso and ADD domain of DNA methyltransferase are essential for complex formation. Thus, Kaiso can affect DNA methylation.

molecular biology↗

TRIM28 regulates Kaiso SUMOylation

Tripartite motif protein 28 (TRIM28), a universal mediator of Kruppel-associated box domain zinc fingers (KRAB-ZNFs), is known to regulate DNA methylation of many repetitive elements and several imprinted loci. TRIM28 serves as a scaffold unit that is essential for the formation of stable repressor complexes. In the present study we found that TRIM28 is a binding partner for methyl-DNA binding protein Kaiso. Kaiso is a transcription factor that belongs to the BTB/POZ -zinc finger family. Recent data suggest that deficiency of Kaiso led to reduction of DNA methylation within the imprinting control region of H19/IGF2. Thus, we hypothesized that Kaiso and TRIM28 may cooperate to control methylated genes. We demonstrated that Kaiso interacts with TRIM28 via its two domains: BTB/POZ and three zinc finger domains. When bound to Kaisos zinc finger domains TRIM28 weakens their interactions with methylated DNA in vitro. Specific association of TRIM28 with BTB/POZ domain causes Kaiso hyperSUMOylation. Altogether our data describe a putative role of TRIM28 as a regulator of Kaiso activity.

molecular biology↗