Impairment of sumoylation and chromatin binding of Kaiso as a result of osmotic stress

In vertebrates Kaiso is involved in cancer progression, cell cycle control, apoptosis and WNT signaling. Regulation of Kaiso activity by extracellular signals may elucidate how environmental events are reflected in transcription. In kidney human cell lines Kaiso predominantly exists as sumoylated (K42 within BTB/POZ domain) protein. In response to osmotic stress (340-800 mosmol/kg) Kaiso undergoes fast (5 min) and dramatic delocalization to numerous nuclear DAPI-less foci and nuclear periphery which is accompanied by loss of sumo. Desumoylation is reversible upon return to isotonicity. Mapping of Kaiso binding sites in vivo suggested that salt treatment immediately impairs its DNA binding, although, desumoylation is sufficient but not enough for stripping Kaiso from chromatin. Response of Kaiso is independent of p38 MAPK, ATM, Src and Erk kinases that make it very similar to insulator body formation in salt treated Drosophila cells. Indeed, in human renal cells hypertonicity results in colocalization of Kaiso, CTCF and PRC1 proteins which form together hypothetical insulator bodies. Thus, Kaiso is a fast sensor of hypertonicity.