ArticleMolecular and cellular biology2005
Identification of cis-regulatory sequences in the human angiotensinogen gene by transgene coplacement and site-specific recombination.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 14 citations in OpenAlex.
- The transgenic IG-DMR sequence of the mouse Dlk1-Dio3 domain acquired imprinted DNA methylation during the post-fertilization period.Epigenetics & chromatin · 2023Article
- Liver and Steroid Hormones-Can a Touch of p53 Make a Difference?Frontiers in endocrinology · 2019Review
- Proteolytic ectodomain shedding of membrane proteins in mammals-hardware, concepts, and recent developments.The EMBO journal · 2018Review
- The PPAR-gamma-binding sequence Pal3 is necessary for basal but dispensable for high-fat diet regulated human renin expression in the kidney.Pflugers Archiv : European journal of physiology · 2017Article
- Analysis and validation of traits associated with a single nucleotide polymorphism Gly364Ser in catestatin using humanized chromogranin A mouse models.Journal of hypertension · 2016Article
- The H19 imprinting control region mediates preimplantation imprinted methylation of nearby sequences in yeast artificial chromosome transgenic mice.Molecular and cellular biology · 2013Article
- Angiotensinogen gene transcription in pulmonary fibrosis.International journal of peptides · 2012Article
- A single nucleotide mutation in the mouse renin promoter disrupts blood pressure regulation.The Journal of clinical investigation · 2008Article
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The function of putative regulatory sequences identified in cell transfection experiments can be elucidated only through in vivo experimentation. However, studies of gene regulation in transgenic mice (TgM) are often compromised by the position effects, in which independent transgene insertions differ in expression depending on their location in the genome. In order to overcome such a dilemma, a method called transgene coplacement has been developed in Drosophila melanogaster. In this method, any two sequences can be positioned at exactly the same genomic site by making use of Cre/loxP recombination. Here we applied this method to mouse genetics to characterize the function of direct repeat (DR) sequences in the promoter of the human angiotensinogen (hAGT) gene, the precursor of the vasoactive octapeptide angiotensin II. We modified a hAGT bacterial artificial chromosome to use Cre/loxP recombination in utero to generate TgM lines bearing a wild-type or a mutant promoter-driven hAGT locus integrated at a single chromosomal position. The expression analyses revealed that DR sequences contribute 50 or >95% to hAGT transcription in the liver and kidneys, respectively, whereas same sequences are not required in the heart and brain. This is the first in vivo dissection of DNA cis elements that are demonstrably indispensable for regulating both the level and cell type specificity of hAGT gene transcription.
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