Open AccessEnrichment of (pro)renin receptor promoter with activating histone codes in the kidneys of spontaneously hypertensive rats
Author(s) -
Hae-Ahm Lee,
Dong-Youb Lee,
HyoJung Lee,
Hyung Soo Han,
Inkyeom Kim
Publication year - 2011
Publication title -
jraas. journal of the renin-angiotensin-aldosterone system/journal of the renin-angiotensin-aldosterone system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.457
H-Index - 46
eISSN - 1752-8976
pISSN - 1470-3203
DOI - 10.1177/1470320311415738
Subject(s) - histone , histone h3 , chromatin immunoprecipitation , microbiology and biotechnology , renin–angiotensin system , histone methylation , endocrinology , methylation , methylated dna immunoprecipitation , medicine , histone code , chemistry , dna methylation , biology , promoter , gene expression , dna , biochemistry , gene , nucleosome , blood pressure
Background: The (pro)renin receptor [(P)RR] non-proteolytically, through conformational change, activates prorenin which can convert angiotensinogen to angiotensin I in addition to the classic conversion of angiotensinogen to angiotensin I by circulating renin. Since renal (P)RR is upregulated in hypertension and implicated in the pathogenesis of malignant hypertension, we hypothesized that (pro)renin receptor promoter is enriched with activating histone codes in the kidney of spontaneously hypertensive rats (SHR). Methods: The mRNA and protein expression levels were measured by real-time polymerase chain reaction (PCR) and western blot, respectively. The DNA methylation status of (P)RR promoter region was analyzed by bisulfite sequencing. The histone modifications were determined by chromatin immunoprecipitation followed by real-time PCR. Results: The (P)RR mRNA expression in the kidney was about six times greater in SHR than in Wistar–Kyoto (WKY) rats. The (P)RR promoter was little methylated in the kidneys of both WKY and SHR. Acetylated histone H3 (H3Ac) and di-methylated histone H3 at lysine 4 (H3K4me2), activating histone codes, were about 25 and three times higher in SHR than in WKY, respectively. On the other hand, di-methylated histone H3 at lysine 9 (H3K9me2), a suppressive histone code, was 50 times lower in SHR than in WKY. Conclusion: These results suggest that the (P)RR promoter is enriched with activating histone codes in the kidneys of SHR.