D. Turgeon et al., Isolation and characterization of the human UGT2B15 gene, localized withina cluster of UGT2B genes and pseudogenes on chromosome 4, J MOL BIOL, 295(3), 2000, pp. 489-504
Glucuronidation is a major pathway of androgen metabolism and is catalyzed
by UDP-glucuronosyltransferase (UGT) enzymes. UGT2B15 and UGT2B17 are 95 %
identical in primary structure, and are expressed in steroid target tissues
where they conjugate C19 steroids. Despite the similarities, their regulat
ion of expression are different; however, the promoter region and genomic s
tructure of only the UGT2B17 gene have been characterizedX to date. To isol
ate the UGT2B15 gene and other novel steroid-conjugating UGT2B genes, eight
P-l-derived artificial chromosomes (PAC) clones varying in length from 30
kb to 165 kb were isolated. The entire UGT2B15 gene was isolated and charac
terized from the PAC clone 21598 of 165 kb. The UGT2B15 and UGT2B17 genes a
re highly conserved, are both composed of six exons spanning approximately
25 kb, have identical exon sizes and have identical exon-intron boundaries.
The homology between the two genes extend into the 5'-flanking region, and
contain several conserved putative cis-acting elements including Pbx-1, C/
EBP, AP-1, Oct-1 and NF/kappa B. However, transfection studies revealed dif
ferences in basal promoter activity between the two genes, which correspond
to regions containing non-conserved potential elements. The high degree of
homology in the 5'-flanking region between the two genes is lost upstream
of -1662 in UGT2B15, and suggests a site of genetic recombination involved
in duplication of UGT2B genes. Fluorescence in situ hybridization mapped th
e UGT2B15 gene to chromosome 4q13.3-21.1. The other PAC clones isolated con
tain exons from the UGT2B4, UGT2B11 and UGT2B17 genes. Five novel exons, wh
ich are highly homologous to the exon 1 of known UGT2B genes, were also ide
ntified; however, these exons contain premature stop codons and represent t
he first recognized pseudogenes of the UGT2B family. The localization of hi
ghly homologous UGT2B genes and pseudogenes as a cluster on chromosome 4q13
reveals the complex nature of this gene locus, and other novel homologous
UGT2B genes encoding steroid conjugating enzymes are likely to be found in
this region of the genome. (C) 2000 Academic Press.