Transcriptional influence of two poly purine-pyrimidine tracts located in the HSD11B2 (11beta-hydroxysteroid dehydrogenase type 2) gene

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Abstract

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 (11β-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.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalEndocrine Research
Volume27
Issue number1-2
DOIs
StatePublished - 2001

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11-beta-Hydroxysteroid Dehydrogenase Type 2
Gene Expression
Reporter Genes
Z-Form DNA
Genes
Luciferases
11-beta-Hydroxysteroid Dehydrogenases
Dinucleotide Repeats
Introns
Exons
pyrimidine
purine

ASJC Scopus subject areas

  • Endocrinology

Cite this

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title = "Transcriptional influence of two poly purine-pyrimidine tracts located in the HSD11B2 (11beta-hydroxysteroid dehydrogenase type 2) gene",
abstract = "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 (11β-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.",
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N2 - 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 (11β-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.

AB - 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 (11β-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.

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