The identification and characterization of KRAB-domain-containing zinc finger proteins

The zinc finger motif is a highly conserved tandemly repeated sequence of 28-30 amino acids that was first identified in transcription factor TFIIIA from Xenopus laevis. Subsequently, similar motifs were found and characterized in many genes from mammalian genomes and the genomes of lower eukaryotes such as Drosophila and yeast, thereby defining a large superfamily of genes. Non-finger-coding modules conserved among members of subfamilies of zinc finger genes have been described in the murine genome (finger-associated boxes, or FAX domain) and the human genome (Krüppel-associated boxes, or KRAB domain). Here we report the identification and partial characterization of more members of the human KRAB-containing subfamily of genes. Based on Southern blot hybridization experiments, they also are zinc-finger-coding genes. All members share a highly homologous 42-amino-acid-long A element of the described KRAB domain. The conservation extends to the murine developmentally expressed zinc finger gene, mKr2. The homologous sequences, however, are part of the 5'-untranslated region. In all cases for which there is adequate information, the KRAB domain is found at the NH2-terminus of the respective protein. In one zinc-finger-encoding cDNA clone that we characterized further in this work, BRc1744 (ZNF45), the KRAB domain most probably constitutes the entire second exon of the gene. Based on the data, it is tempting to speculate that the FAX- and KRAB-containing zinc finger genes define subfamilies of genes with overlapping functions that participate in the regulation of common or similar developmental programs.