Abstract 102: Targeted Disruption Of Ctcf Binding Near The Ren Gene Alters Local Gene Expression In Response To Dietary Salt

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2023-09, Vol.80 (Suppl_1)
• Main Authors: Vanden Avond, Mark, Grzybowski, Michael, Kurth, Terry, Greene, Andrew, Liang, Mingyu, Cowley, Allen, Geurts, Aron M
• Format: Article
• Language: English
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/hyp.80.suppl_1.102

Abstract only Blood pressure regulation and hypertension risk may be impacted by changes in chromatin conformation (CC) caused by common genetic variations. CCCTCF-binding factor (CTCF) is a DNA architecture protein that regulates CC and thereby gene expression. We hypothesized that disruption of local CC surrounding the renin gene can alter local gene expression and influence blood pressure changes to dietary salt. Three mutant rat models were created using CRISPR-Cas9 in the Dahl salt-sensitive rat with mutations in one or more CTCF motifs surrounding the renin gene. Disruption of CTCF binding was confirmed at specific mutated sites in all three models. Plasma renin activity (PRA) was measured and RNA-seq analysis was performed in multiple tissues of wild-type (WT) and mutant rats fed a 0.1%, 0.4% or 4.0% NaCl diet for four days. While PRA in WT males responded as expected (17.52±0.81, 12.87±1.00, and 7.13±0.19 ng/mL; p