S49-2 Aldosterone Biosynthesis Mediated by the Epigenetic Regulation

Program: Symposia
Session: S49-Inside and Out: Aldosterone Synthesis and Action
Translational
Monday, June 17, 2013: 9:00 AM-10:30 AM
Presentation Start Time: 9:30 AM
Room 304 (Moscone Center)
Yoshiyu Takeda*
Kanazawa University, Kanazawa, Japan
Talk Description:

I talk about novel control mechanisms for the CYP11B2 (aldosterone synthase) gene in the adrenal and cardiovascular tissues mediated by the epigenetic regulation. CpG dinucleotides in CYP11B2 promoter were found to be hypermethylated in tissues with low expression but not those with high expression of CYP11B2. Methylation of CYP11B2 promoter fused to a reporter gene decreased transcriptional activity. Methylation of recognition sequences of transcription factors, including CREB1, NGFIB (NR4A1) and NURR1 (NR4A2) diminished their DNA-binding activity. A methylated-CpG-binding protein MECP2 interacted directly with the methylated CYP11B2 promoter. The methylation was low in the zona glomerulosa, a major site of aldosterone secretion compared to the other two zones of fasciculata and reticularis in the human adrenal cortex. CYP11B2 mRNA levels were inversely correlated with CYP11B2 methylation in human myocardium. These results suggest an epigenomic mechanism affecting this gene causally linked with aldosterone synthesis in cardiovascular diseases.