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Retinoic acid‐induced regulation of guanylyl cyclase/natriuretic peptide receptor‐A gene expression in gene‐targeted mice via histone H3 modifications
Author(s) -
Kumar Prerna,
Periyasamy Ramu,
Das Subhankar,
Pandey Kailash N
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1189.5
Subject(s) - npr1 , histone deacetylase , histone deacetylase 5 , npr2 , histone , histone h3 , retinoic acid receptor , acetylation , histone deacetylase 2 , retinoic acid , endocrinology , medicine , natriuretic peptide , chemistry , biology , biochemistry , gene , heart failure
Guanylyl cyclase/natriuretic peptide receptor‐A (GC‐A/NPRA) is the biological receptor of cardiac hormones atrial and brain natriuretic peptides (ANP and BNP), which plays an important role in maintaining renal and cardiovascular homeostasis. Present study was designed to uncover the regulatory mechanism involved in Npr1 gene (coding for GC‐A/NPRA) transcription by all‐trans retinoic acid (ATRA) and histone deacetylase (HDAC) inhibitor sodium butyrate (NaBu) in Npr1 gene‐targeted mice. Mice (16‐week old) were injected intraperitonealy with ATRA (0.5 mg/Kg/day), NaBu (0.5 mg/Kg/day), and ATRA‐NaBu (1.0 mg/Kg/day) for 2‐week. The results showed that renal HDAC activity was increased and acetylated histone levels were decreased in gene‐knockout heterozygous (1‐copy; Npr1+/−) mice compared with wild‐type (2‐copy; Npr1+/+) mice; however, HDAC activity was decreased in gene‐duplicated (3‐copy; Npr1++/+) mice. A significant increase in acetylation of histone H3 and H4 and reduction in HDAC activity was observed in ATRA‐ and NaBu‐treated animals. ATRA and NaBu cooperatively activated renal Npr1 mRNA levels by 3‐fold in 1‐copy and 3.5‐fold in 2‐copy mice. The present results indicate that ATRA epigenetically regulates Npr1 gene in vivo via histone modifications and should have important implications in renal and cardiovascular events in disease states. This work was supported by the NIH grant (HL62147).