Transcriptional influence of two poly purine-pyrimidine tracts located in the HSD11B2 (11beta-hydroxysteroid dehydrogenase type 2) gene.
Alternating purine-pyrimidine (APP) sequences which might assume left handed DNA helical structures (Z-DNA) could influence the expression of genes in which they were located. There are two such repeat elements in the HSD11B2 (11beta-hydroxysteroid dehydrogenase) gene. First, a CA repeat is located in the first intron. Deletion of this element in a minigene construct leads to a significant decrease (40%) in the expression of the HSD11B2 message in human cortical collecting duct cells. The second APP tract is located approximately 0.9 kb from the last exon or 4.8 kb from the intronic CA repeat element. Deleting this APP tract in a minigene decreases gene expression by 30%. The CA repeat along with its flanking sequences increases luciferase reporter gene expression if placed 5' of the HSD11B2 promoter but not when placed downstream of the reporter gene. Similarly the second APP tract increases luciferase reporter gene expression when placed 5' of the HSD11B2 promoter in an antisense orientation but not in a sense orientation. These results suggests that these dinucleotide repeats influence expression of the HSD11B2 gene in a manner dependent on position and orientation.
Agarwal
A K
AK
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75390-9063, USA. aagarw@mednet.swmed.edu
D042842:11-beta-Hydroxysteroid Dehydrogenases; D001483:Base Sequence; D002478:Cells, Cultured; D004247:DNA / Q000737:chemistry; D017353:Gene Deletion; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000235:genetics*; D007438:Introns; D007685:Kidney Tubules, Collecting; D008156:Luciferases / Q000235:genetics; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011687:Purines / Q000737:chemistry*; D011743:Pyrimidines / Q000737:chemistry*; D011994:Recombinant Proteins; D012091:Repetitive Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014162:Transfection
D011687:Purines; D011743:Pyrimidines; D011994:Recombinant Proteins; D004247:DNA; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D008156:Luciferases