Characterization and expression of a human KCTD1 gene containing the BTB domain, which mediates transcriptional repression and homomeric interactions

We identified potassium channel tetramerization domain-containing 1 (KCTD1) gene in a human brain cDNA library. Here, we report that the KCTD1 gene contains seven exons, encoding 257 amino acid residues with a predicted molecular mass of 29.4 kDa. Sequence alignments showed KCTD1 protein contains an N-terminal broad-complex, tramtrack, and bric-a-brac (BTB) domain. Northern blot analysis revealed that KCTD1 is expressed in the mammary gland, kidney, brain, and ovary compared to other tissues. Further, the subcellular localization results showed that KCTD1 is localized in the nuclei of HeLa and HBL100 cells. Reporter gene assays in HEK293FT and NIH3T3 cells further indicated that KCTD1 acts as a potent transcriptional repressor and inhibits the transcriptional activity via its BTB domain, though KCTD1 transcriptional repression is unaffected by the HDAC inhibitors, trichostatin A, and sodium butyrate. Finally, we found that the BTB domain of KCTD1 mediates homomeric protein-protein interactions by co-immunoprecipitation and GST pull-down assays. These data present the first characterization of human KCTD1 and suggest that KCTD1 is a nuclear protein that functions as a transcriptional repressor and mediates protein-protein interactions through a BTB domain.