Expression of T : G mismatch-specific thymidine-DNA glycosylase and DNA methyl transferase genes during development and tumorigenesis

Abstract

In situ hybridization was used to characterize the expression pattern of the T : G mismatch-specific thymidine-DNA glycosylase (TDG) gene, encoding a DNA repair enzyme which corrects G : T mismatches that result from the hydrolytic deamination of 5-methyl cytosines. TDG transcripts were uniformly and ubiquitously expressed from 7.5–13.5 days post-coitum, but were then markedly enriched in specific tissues of the developing fetus. At 14.5 gestational days, TDG was strongly expressed in the developing nervous system, thymus, lung, liver, kidney and intestine. At later stages, high levels of expression were detected in the thymus, brain, nasal epithelium and within proliferating regions of the intestine, skin, kidney, teeth and bone. This pattern of expression strongly correlated with those of the methyl transferase (MTase) gene, coding for the enzyme which specifically methylates CpG dinucleotides, and the p53 tumour suppressor gene. However, TDG and MTase were differentially expressed during maturation of the male and female germline. We also report that tumors occuring in mice which overexpress MMTV-v-Ha-ras or MMTV-c-myc transgenes or mice heterozygous for p53 gene disruption, all show elevated TDG and MTase expression specific to the transformed tissue.