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 k b including the promoter. UNG comprises 6 exons and 5 introns and was assigned to chromosome 12q23-q24.1 by radiation hybrid mapping. UNG ex hibits 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 number of elements involved in constitutive expression and cell cycle regula tion. A smaller CpG island is located just downstream of the gene. Wit hin the 15-kb sequence we identified 16 Alu retroposons, 2 of which co ntain putative competent RNA polymerase III promoters, 3 copies of med ium reiteration frequency repeats, and 1 copy of a mammalian-wide inte rspersed repetitive element, as well as a 300-bp TA-dinucleotide repea t. In vitro methylation of the UNG promoter strongly reduced promoter activity, but methylation may not be involved in regulation of UNG in vivo since a narrow region of the 5' CpG island comprising the putativ e transcription factor binding region appears to be invariably methyla tion-free. (C) 1996 Academic Press, Inc.