The POZ-ZF transcription factor Znf131 is implicated as a regulator of Kaiso-mediated biological processes

Znf131 belongs to the family of POZ-ZF transcription factors, but, in contrast to most other characterized POZ-ZF proteins that function as transcriptional repressors, Znf131 acts as a transcriptional activator. Znf131 heterodimerizes with the POZ-ZF protein Kaiso, which itself represses a subset of canonical Wnt target genes, including the cell cycle regulator Cyclin D1. Herein, we report a possible role for Znf131 in Kaiso-mediated processes. Notably, we found that Znf131 associates with several Kaiso target gene promoters, including that of CCND1. ChIP analysis revealed that Znf131 indirectly associates with the CCND1 promoter in HCT116 and MCF7 cells via a region that encompasses the previously characterized +69 Kaiso Binding Site, hinting that the Znf131/Kaiso heterodimer may co-regulate Cyclin D1 expression. We also demonstrate that Kaiso inhibits Znf131 expression, raising the possibility that Kaiso and Znf131 act to fine-tune target gene expression. Together, our findings implicate Znf131 as a co-regulator of Kaiso-mediated biological processes. •Given protein interactions with Znf131 & Kaiso, Znf131 hypothesized to co-regulate Kaiso biological processes.•Znf131 indirectly interacts with Kaiso target genes, including CCND1, via association with Kaiso.•Znf131 overexpression increases CCND1 promoter activity & Cyclin D1 protein levels.•Inverse Znf131 & Kaiso expression in intestinal cells & Kaiso-transgenic mice, but positive correlation in colon cancer.•Kaiso & Znf131 may antagonize or synergize with one another depending on homeostatic contexts.