Epigenetic and Transcriptional regulation of the Human Angiotensinogen Gene by High Salt
Document Type
Dataset
Publication Date
9-19-2023
Abstract
Hypertension is caused by a combination of genetic and environmental factors. Angiotensinogen (AGT) is a component of RAAS, that regulates blood pressure. The human AGT (hAGT) gene has -6A/-6G polymorphism and -6A variant is associated with human hypertension. In this study, we have investigated the epigenetic regulation of the hAGT gene. To understand transcriptional regulation of the hAGT, we have made transgenic animals containing -6A. We show that HS affects DNA methylation and modulates transcriptional regulation of this gene in liver and kidney. HS increases hAGT gene expression in -6A TG mice. We have observed that the number of CpG sites in the hAGT promoter is decreased after HS treatment. In the liver, four CpG sites are methylated whereas after HS treatment, only two CpG sites observed. In the kidney, five CpG sites are methylated, whereas after HS treatment, only three CpG sites are observed. These results suggest that HS promotes DNA demethylation and increasing AGT gene expression. RT-PCR and immunoblot analysis show that hAGT gene expression is increased after HS treatment. Chip assay has shown that transcription factors bind strongly after HS treatment. RNA-Seq analysis identified differentially expressed genes, canonical pathways, upstream regulators. One of the plausible mechanisms for HS induced up-regulation of the hAGT gene is through IL-6/JAK/STAT3/AGT axis.
To understand the epigenetic and transcriptional regulation of hAGT gene we have made transgenic animals containing -6A.
We gave high salt to mice and collected liver and kidney tissues. We isolated RNA and did RNA Seq analysis in liver and kidney tissues.
We then performed gene expression profiling analysis using data obtained from RNA-seq.
We further identified top canonical pathways, top diseases and functions and upstream regulators by using Ingenuity Pathway Analysis.
Repository
NCBI Gene Expression Omnibus
Recommended Citation
Perla, S., & Kumar, A. (2023). Epigenetic and Transcriptional regulation of the Human Angiotensinogen Gene by High Salt. Retrieved from https://touroscholar.touro.edu/touro_data/6
