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) fo rms of uracil-DNA glycosylase. The gene contains seven exons organised like the human counterpart. While the putative Ung1 promoter (P-B) and the huma n P-B contain essentially the same, although differently organised, transcr iption factor binding elements, the Ung2 promoter (P-A) shows limited homol ogy to the human counterpart. Transient transfection of chimaeric promoter- luciferase constructs demonstrated that both promoters are functional and t hat 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 e xpressed. Furthermore, transcription of both mRNA forms, particularly Ung2, is induced in mid-gestation embryos. Except for a strong conservation of t he 26 N-terminal residues in Ung2, the subcellular targeting sequences in t he encoded proteins have limited homology. Ung2 is transported exclusively to the nucleus in NIH 3T3 cells as expected. In contrast, Ung1 was sorted b oth to nuclei and mitochondria. These results demonstrate that although the catalytic domain of uracil-DNA glycosylase is highly conserved in mouse an d man, regulatory elements in the gene and subcellular sorting sequences in the proteins differ both structurally and functionally, resulting in alter ed contribution of the isoforms to total uracil-DNA glycosylase activity.