Analysis of uracil-DNA glycosylases from the murine Ung gene reveals differential expression in tissues and in embryonic development and a subcellular sorting pattern that differs from the human homologues

The murine Ung gene encodes both mitochondrial (Ung1) and nuclear (Ung2) forms of uracil-DNA glycosylase. The gene contains seven exons organised like the human counterpart. While the putative Ung1 promoter (P-B) and the human P-B contain essentially the same, although differently organised, transcription factor binding elements, the Ung2 promoter (P-A) shows limited homology to the human counterpart. Transient transfection of chimaeric promoter-luciferase constructs demonstrated that both promoters are functional and that P-B drives transcription more efficiently than P-A. mRNAs for Ung1 and Ung2 are found in all adult tissues analysed, but they are differentially expressed. Furthermore, transcription of both mRNA forms, particularly Ung2, is induced in mid-gestation embryos. Except for a strong conservation of the 26 N-terminal residues in Ung2, the subcellular targeting sequences in the encoded proteins have limited homology. Ung2 is transported exclusively to the nucleus in NIH 3T3 cells as expected. In contrast, Ung1 was sorted both to nuclei and mitochondria. These results demonstrate that although the catalytic domain of uracil-DNA glycosylase is highly conserved in mouse and man, regulatory elements in the gene and subcellular sorting sequences in the proteins differ both structurally and functionally, resulting in altered contribution of the isoforms to total uracil-DNA glycosylase activity.