Key result
The intron 16 deletion of the ACE gene showed no significant difference compared to the insertion form in affecting heterologous promoter activity in an in vitro assay system.
Why the study?
Does the intron 16 deletion of the ACE gene act as a transcriptional silencer in ACE expressing cells?
Does the intron 16 deletion of the ACE gene act as a transcriptional silencer in ACE expressing cells?
The intron 16 deletion of the ACE gene does not appear to regulate transcription by acting as a silencer in this in vitro assay system.
In vitro data refute a silencer role for the ACE intron 16 deletion; leaves open alternative mechanisms for its clinical associations.
BACKGROUND: The insertion/deletion (I/D) polymorphism in intron 16 of angiotensin converting enzyme (ACE) is associated with circulating and tissue enzymatic levels, around two-fold higher in homozygous D than homozygous I individuals. The mechanism underlying this quantitative difference is unknown and the hypothesis that the deletion removes a transcriptional silencer located within the intron has been proposed. METHODS: We have set up an assay based on constructs carrying fragments of intron 16, either in the I or in the D form, fused to the Herpes simplex virus thymidine kinase heterologous promoter driving the expression of the CAT reporter gene. These constructs have been used in transfection experiments in ACE expressing cells. RESULTS: Plasmids containing either intronic fragments from I and D subjects or an artificial D fragment derived from an I intron did not show significant difference between I and D in affecting the heterologous promoter activity. The finding of a yet undescribed polymorphism in intron 16 is also reported. CONCLUSION: The above results suggest that the intron 16 deletion by itself has no effect in regulating transcription in our assay system.
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Nadia Rosatto (1999) studied Angiotensin converting enzyme (ACE) gene polymorphism. Intron 16 deletion (D form) constructs vs. Intron 16 insertion (I form) constructs was evaluated on Heterologous promoter activity (CAT reporter gene expression). The intron 16 deletion of the ACE gene showed no significant difference compared to the insertion form in affecting heterologous promoter activity in an in vitro assay system.
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