Disruption of local CTCF binding impairs renin expression and blood pressure response in Dahl salt-sensitive rats [Region Capture Micro-C]

ABSTRACT: CCCTCF-binding factor (CTCF) is a DNA binding protein with multiple functions to regulate gene expression, including establishing and maintaining chromatin conformation. The Ren gene is surrounded by multiple conserved CTCF-binding motifs and, while complete loss of CTCF has been demonstrated to be critical for normal Ren expression, whether disruption of a specific motif is sufficient to alter blood pressure is still unknown. We created a rat model with a mutation to a CTCF binding site within the first intron of the Ren gene in the Dahl SS rat. CTCF binding was disrupted and local chromatin interactions near the Ren gene promoter were altered. No local genes were dysregulated in kidney cortex by bulk RNA-seq on any diet. Interestingly, plasma renin activity failed to increase in the mutant males in response to a salt depleted diet. Concurrently, mutant males had lower blood pressure during first three of days of dietary salt restriction. Though no differences in kidney Ren mRNA or protein distribution expression were detected at this time point in vivo, the increase in response to salt depletion was acutely impaired in cultured mutant kidney slices for at least 12 hours compared to wild-type controls. This is the first demonstration that a mutation to a specific CTCF binding site is sufficient to depress the initial renin response to salt depletion, blunt plasma renin activity, and ultimately impair the blood pressure response to a salt depleted state in vivo.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE293393 | GEO | 2026/09/22

REPOSITORIES: GEO