CRTR-1, a developmentally regulated transcriptional repressor related to the CP2 family of transcription factors

CP2-related proteins comprise a family of DNA-binding transcription factors that are generally activators of transcription and expressed ubiquitously. We reported a differential display polymerase chain reaction fragment, Psc 2, which was expressed in a regulated fashion in mouse pluripotent cells in vitro and in vivo. Here, we report further characterization of the Psc2 cD NA and function. The Psc2 cDNA contained an open reading frame homologous t o CP2 family proteins. Regions implicated in DNA binding and oligomeric com plex formation, but not transcription activation, were conserved. Psc2 expr ession in vivo during embryogenesis and in the adult mouse demonstrated tig ht spatial and temporal regulation, with the highest levels of expression i n the epithelial lining of distal convoluted tubules in embryonic and adult kidneys. Functional analysis demonstrated that PSC2 repressed transcriptio n 2.5-15-fold when bound to a heterologous promoter in ES, 293T, and COS-l cells. The N-terminal 52 amino acids of PSC2 were shown to be necessary and sufficient for this activity and did not share obvious homology with repor ted repressor motifs. These results represent the first report of a CP2 fam ily member that is expressed in a developmentally regulated fashion in vivo and that acts as a direct repressor of transcription. Accordingly, the pro tein has been named CP2-Related Transcriptional Repressor-1 (CRTR-1).