Human uracil-DNA glycosylase gene: sequence organization, methylation pattern, and mapping to chromosome 12q23-q24.1

The human uracil-DNA glycosylase gene (UNG) spans approximately 13.5 kb including the promoter. UNG comprises 6 exons and 5 introns and wa s assigne chromosome 12q23-q24.1 by radiation hybrid mapping. UNG exh ibits typical features of housekeeping genes, including a 5' CpG isla nd of 1.2 kb and a very GC-rich TATA-less promoter containing a numbe r of elements involved in constitutive expression and cell cycle regu lation. A smaller CpG island is located just downstream of the gene. Within the 15-kb sequence we identified 16 Alu retroposons, 2 of whic h contain putative competent RNA polymerase III promoters, 3 copies o f medium reiteration frequency repeats, and 1 copy of a mammalian-wid e interspersed repetitive element, as well as a 300-bp TA-dinucleotid e repeat. In vitro methylation of the UNG promoter strongly reduced p romoter activity, but methylation may not be involved in regulation o f UNG in vivo since a narrow region of the 5' CpG island comprising t he putative transcription factor binding region appears to be invaria bly methylation-free.