title: Enrichment of (pro)renin receptor promoter with activating histone codes in the kidneys of spontaneously hypertensive rats.
abstract: 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.
  
  
  CONCLUSIONS
  These results suggest that the (P)RR promoter is enriched with activating histone codes in the kidneys of SHR.
authors.affiliation: Department of Pharmacology, Kyungpook National University School of Medicine, Daegu, Korea.
authors.forename: Hae-Ahm
authors.initials: HA
authors.lastname: Lee
authors.forename: Dong-Youb
authors.initials: DY
authors.lastname: Lee
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hyung Soo
authors.initials: HS
authors.lastname: Han
authors.forename: InKyeom
authors.initials: I
authors.lastname: Kim
mesh_terms: D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D044127:Epigenesis, Genetic; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D042421:Histone Code / Q000235:genetics*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics*; D012083:Renin / Q000235:genetics / Q000378:metabolism; D000093342:Prorenin Receptor
chemical_list: D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D011956:Receptors, Cell Surface; D000808:Angiotensinogen; D051548:Histone Acetyltransferases; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D006655:Histone Deacetylases; D000093342:Prorenin Receptor