Artikel
Differences in Enhancer activity of the 11-15 kb upstream non-coding region in transcriptional regulation of the human renin gene in different cellular models
Unterschiede in der Enhancer Aktivität der 11-15kb upstream nicht kodierenden Region des humanen Renin Gens in unterschiedlichen Zellsystemen
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Veröffentlicht: | 8. August 2006 |
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Gliederung
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Our project contributes to our understanding by exploring the complexity of the transcriptional regulation of the human renin gene. The protease renin is one key regulatory element in the renin-angiotensin-aldosteron system (RAAS). The RAAS is essential for the regulation of blood pressure and electrolyte balance in mammals. The knowledge about the fundamental mechanisms is therefore of great importance for the understanding of both normal physiology and the development of diseased states, such as hypertension and heart failure.
In a previous work we have shown that there is theoretical evidence of potential regulatory importance based on a binding profile in a conserved 3.9-kb-long hRENc DNA block approx. 11 kb upstream of the renin gene. To verify the predictions, we have cloned fragments, each of approximately 700 bp size of the region originally 11-15 kb upstream of the human renin gene together with the canonical renin promoter into pGL3-luciferase constructs. These DNA-constructs show different characteristic luciferase activity profiles when transfected into different developmental models, namely Human Embryonic Kidney Cells (293), an adult renin producing cell line, and HT1080 cell line (control), which strongly suggests a functional relevance of these DNA regions during development.