TY - JOUR
T1 - Human uroporphyrinogen-III synthase
T2 - Genomic organization, alternative promoters, and erythroid-specific expression
AU - Aizencang, Gerardo
AU - Solis, Constanza
AU - Bishop, David F.
AU - Warner, Cecilia
AU - Desnick, Robert J.
N1 - Funding Information:
The authors thank Drs. S.-F. Tsai, Andrew Roberts, Weiming Xu, and Luis Cunha for their contributions to isolate and characterize the human URO-synthase gene and Dr. Kenneth H. Astrin for valuable assistance with the manuscript. This research was supported in part by grants from the National Institutes of Health, including a research grant (5 R01 DK26824), a grant (5 P30 HD28822) for the Mount Sinai Children’s Health Research Center, and a grant (2 M01 RR00071) for the Mount Sinai General Clinical Research Center from the National Center for Research Resources.
PY - 2000/12/1
Y1 - 2000/12/1
N2 - Uroporphyrinogen-III (URO) synthase is the heme biosynthetic enzyme defective in congenital erythropoietic porphyria. The ~34-kb human URO-synthase gene (UROS) was isolated, and its organization and tissue-specific expression were determined. The gene had two promoters that generated housekeeping and erythroid-specific transcripts with unique 5'-untranslated sequences (exons 1 and 2A) followed by nine common coding exons (2B to 10). Expression arrays revealed that the housekeeping transcript was present in all tissues, while the erythroid transcript was only in erythropoietic tissues. The housekeeping promoter lacked TATA and SP1 sites, consistent with the observed low level expression in most cells, whereas the erythroid promoter contained GATA1 and NF-E2 sites for erythroid specificity. Luciferase reporter assays demonstrated that the housekeeping promoter was active in both erythroid K562 and HeLa cells, while the erythroid promoter was active only in erythroid cells and its acitvity was increased during heroin-induced erythroid differentiation. Thus, human URO-synthase expression is regulated during erythropoiesis by an erythroid-specific alternative promoter. (C) 2000 Academic Press.
AB - Uroporphyrinogen-III (URO) synthase is the heme biosynthetic enzyme defective in congenital erythropoietic porphyria. The ~34-kb human URO-synthase gene (UROS) was isolated, and its organization and tissue-specific expression were determined. The gene had two promoters that generated housekeeping and erythroid-specific transcripts with unique 5'-untranslated sequences (exons 1 and 2A) followed by nine common coding exons (2B to 10). Expression arrays revealed that the housekeeping transcript was present in all tissues, while the erythroid transcript was only in erythropoietic tissues. The housekeeping promoter lacked TATA and SP1 sites, consistent with the observed low level expression in most cells, whereas the erythroid promoter contained GATA1 and NF-E2 sites for erythroid specificity. Luciferase reporter assays demonstrated that the housekeeping promoter was active in both erythroid K562 and HeLa cells, while the erythroid promoter was active only in erythroid cells and its acitvity was increased during heroin-induced erythroid differentiation. Thus, human URO-synthase expression is regulated during erythropoiesis by an erythroid-specific alternative promoter. (C) 2000 Academic Press.
UR - https://www.scopus.com/pages/publications/0034548040
U2 - 10.1006/geno.2000.6373
DO - 10.1006/geno.2000.6373
M3 - Article
C2 - 11112350
AN - SCOPUS:0034548040
SN - 0888-7543
VL - 70
SP - 223
EP - 231
JO - Genomics
JF - Genomics
IS - 2
ER -