TRIM28 regulates transcriptional activity of methyl-DNA binding protein Kaiso by SUMOylation

Kaiso is a methyl DNA binding transcriptional factor involved in cell cycle control, WNT signaling, colon inflammation, and cancer progression. Recently, it was shown that SUMOylation dynamically modulates the transcriptional activity of Kaiso. However, factors involved in SUMOylation of Kaiso are unknown. Here we show that TRIM28 enhances SUMOylation of Kaiso leading to a decreased methyl-dependent repression ability. TRIM28 is a scaffold protein that regulates transcription and posttranslational modifications of factors involved in cell cycle progression, DNA damage, and viral gene expression. It has SUMO and ubiquitin E3 ligase activity. Here, we defined the domains involved in Kaiso-TRIM28 interaction. The RBCC domain of TRIM28 interacts with the BTB/POZ domain and the zinc fingers of Kaiso. The PHD-bromodomain of TRIM28 is sufficient for the interaction with zinc fingers of Kaiso. Additionally, we found that Kaiso enhances SUMOylation of TRIM28. Altogether our data suggest self-enhancement of SUMOylation of both Kaiso and TRIM28 that affects transcriptional activity of Kaiso.