Chorionic enhancer is dispensable for regulated expression of the human renin gene.
We tested the hypothesis that a transcriptional chorionic enhancer (CE), previously identified to increase human renin expression in choriodecidual cells is required to mediate tissue-specific, cell-specific, and regulated expression of human renin in transgenic mice. Recombineering was used to delete the CE upstream of the renin gene alone or in combination with the kidney enhancer (KE) in a large artificial chromosome construct containing the entire human renin gene and extensive flanking sequences. Deletion of the CE had no qualitative or quantitative effect on the tissue-specific expression of human renin, nor on the cellular localization of human renin in the kidney or placenta. Combined deletion of both the CE and KE caused a decrease in the level of renal renin expression consistent with the established role of the KE. We also considered the possibility that the CE is a downstream enhancer of the KiSS1 gene, which lies directly upstream of renin and is also expressed in the placenta. Deletion of the CE alone, or the CE and KE together, had no effect on the level of KiSS1 expression in the placenta. These data provide convincing evidence that the CE is silent in vivo, at least in the mouse. The absence of a phenotype caused by deletion of the CE is consistent with the observation that the sequence is not evolutionarily conserved.
Zhou
Xiyou
X
Molecular and Cellular Biology Graduate Program, University of Iowa, Iowa City, IA 52242, USA.
Sigmund
Curt D
CD
D000818:Animals; D002823:Chorion / Q000502:physiology*; D022201:Chromosomes, Artificial; D004742:Enhancer Elements, Genetic / Q000502:physiology*; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000502:physiology; D059648:Kisspeptins; D051379:Mice; D008822:Mice, Transgenic; D010920:Placenta / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology; D011506:Proteins / Q000235:genetics; D012083:Renin / Q000235:genetics* / Q000378:metabolism; D019076:Transgenes / Q000502:physiology
C491407:Kiss1 protein, mouse; D059648:Kisspeptins; D011506:Proteins; D012083:Renin