Molecular and Epigenetic Control of Aldosterone Synthase, CYP11B2 and 11-Hydroxylase, CYP11B1

Abstract

Aldosterone and cortisol serve important roles in the pathogenesis of cardiovascular diseases and metabolic disorders. Epigenetics is a mechanism to control enzyme expression by genes without changing the gene sequence. Steroid hormone synthase gene expression is regulated by transcription factors specific to each gene, and methylation has been reported to be involved in steroid hormone production and disease. Angiotensin II or potassium regulates the aldosterone synthase gene, CYP11B2. The adrenocorticotropic hormone controls the 11b-hydroxylase, CYP11B1. DNA methylation negatively controls the CYP11B2 and CYP11B1 expression and dynamically changes the expression responsive to continuous stimulation of the promoter gene. Hypomethylation status of the CYP11B2 promoter region is seen in aldosterone-producing adenomas. Methylation of recognition sites of transcription factors, including cyclic AMP responsive element binding protein 1 or nerve growth factor-induced clone B, diminish their DNA-binding activity. A methyl-CpG-binding protein 2 cooperates directly with the methylated CpG dinucleotides of CYP11B2. A low-salt diet, treatment with angiotensin II, and potassium increase the CYP11B2 mRNA levels and induce DNA hypomethylation in the adrenal gland. A close association between a low DNA methylation ratio and an increased CYP11B1 expression is seen in Cushing’s adenoma and aldosterone-producing adenoma with autonomous cortisol secretion. Epigenetic control of CYP11B2 or CYP11B1 plays an important role in autonomic aldosterone or cortisol synthesis.

Epigenetic alterations of 11beta-hydroxysteroid dehydrogenase 1 gene in the adipose tissue of patients with primary aldosteronism

“…We reported that the hypomethylation status of CYP11B2 is negatively correlated with its mRNA level in APA [24]. CYP11B1 gene expression is also controlled by methylation in the adrenal gland [42]. Inder et al [8] reported a negative correlation between changes in the methylation status and mRNA level of HSD11B1 in the skeletal muscle of diabetic patients.…”

Epigenetics of hypertension as a risk factor for the development of coronary artery disease in type 2 diabetes mellitus

“…Research has also demonstrated that DNA methylation in promoters can be modulated to enable the expression of genes such as Cytochrome P450 Family 11 Subfamily B Member 2 (CYP11B2), which plays a significant role in blood pressure regulation ( 69 ). In spontaneous hypertensive rats, hypomethylation in the gene promoter of the cotransporter, Na+/K+/2Cl (NKCC), leads to an increase in NKCC levels, correlated with postnatal hypertension.…”

Molecular mechanism of flower color formation in Rhododendron simsii Planchon revealed by integration of microRNAome and RNAomics

“…Several hundred genes associated with ower color formation, containing transcription factors, transcriptional co-regulators, proteins involved in epigenetic control of gene expression, and microRNAs, have been well identi ed in model plant (Selva et al 2021; Guan et al 2021;Ren et al 2021;Takeda et al 2023). MicroRNAs (miRNA), a class of non-coding single strand molecules negatively regulating gene expressions both at transcriptional and posttranscriptional levels via cleaving targets or repressing protein translation, play important roles in ower organ development (Takeda et al 2023; Allahverdy and Rashidi 2023). Particularly, functional mature miRNAs are incorporated into Argonaute 1 (AGO1)-containing RNA-induced silencing complex (RISC) target endogenous transcripts, and cause mRNA degradation or translational repression in a sequence-speci c manner (Abel et al 2022).…”

“…Flower color, important objective in ornamental plant breeding, are controled by integrated effects of pigment composition, pH, cell shape, and copigmentation (Sinopoli et al 2019; Wang et al 2023;Li et al 2023). Several hundred genes associated with ower color formation, containing transcription factors, transcriptional co-regulators, proteins involved in epigenetic control of gene expression, and microRNAs, have been well identi ed in model plant (Selva et al 2021; Guan et al 2021;Ren et al 2021;Takeda et al 2023). MicroRNAs (miRNA), a class of non-coding single strand molecules negatively regulating gene expressions both at transcriptional and posttranscriptional levels via cleaving targets or repressing protein translation, play important roles in ower organ development (Takeda et al 2023; Allahverdy and Rashidi 2023).…”