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06:27
Analysis of Cardiac Chamber Development During Mouse Embryogenesis Using Whole Mount Epifluorescence
Published on: April 17, 2019
Characterization of promoter elements required for cardiac chamber-specific expression
T Majalahti1, H Tokola, H Ruskoaho
1Department of Physiology, Institute of Biomedicine, Biocenter Oulu, University of Oulu, Oulu, Finland.
Molecular and Cellular Endocrinology
|June 16, 2009
Summary
A small promoter fragment from rat brain natriuretic peptide (BNP) dramatically enhanced salmon cardiac natriuretic peptide (sCP) gene expression in rat heart cells. This finding suggests BNP promoter elements can convert A-type natriuretic peptide regulation to B-type regulation.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Gene Regulation
Background:
- Salmon cardiac natriuretic peptide (sCP) is a heart-specific gene, serving as a model for cardiac chamber-specific gene expression.
- Its promoter is active in atrial cells but not ventricular cells in mammals.
- Understanding the regulatory mechanisms of natriuretic peptides is crucial for cardiovascular research.
Purpose of the Study:
- To investigate the regulatory elements of the sCP promoter.
- To determine if sequences from the rat brain natriuretic peptide (BNP) promoter can alter sCP gene expression in ventricular cells.
- To explore the potential for transforming A-type natriuretic peptide (ANP) regulation to B-type natriuretic peptide (BNP) regulation.
Main Methods:
- Construction of hybrid luciferase reporter genes using sCP and BNP 5' promoter sequences.
- Transfection of these constructs into rat ventricular cardiomyocytes.
- Measurement of luciferase activity to assess promoter function.
- Analysis of gene expression changes in response to mechanical load and endothelin-1.
Main Results:
- A short rat BNP proximal promoter fragment significantly increased basal activity (100-fold) of the sCP promoter in rat ventricular cardiomyocytes.
- The addition of the BNP fragment also conferred inducibility by mechanical load and endothelin-1.
- These results indicate a transformation of sCP regulation from A-type to B-type natriuretic peptide characteristics.
Conclusions:
- A small BNP promoter fragment can override the native low expression of sCP in ventricular cardiomyocytes.
- This suggests that specific promoter elements, rather than widespread repressors, primarily account for the low expression of A-type natriuretic peptides in ventricular cells.
- These findings have implications for understanding cardiac gene regulation and developing therapeutic strategies.
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