Effect of potassium on DNA methylation of aldosterone synthase gene

Takeda, Y.; Demura, Masashi; Wang, Fen; Yoneda, Takashi; Kometani, Mitsuhiro; Aomo, Daisuke; Hashimoto, Atsushi; Horike, Shin‐ichi; Meguro‐Horike, Makiko; Takeda, Yoshiyu

doi:10.1097/hjh.0000000000002742

Cited by 4 publications

(5 citation statements)

References 25 publications

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“…For a more in-depth understanding of these DEGs, we analyzed the selected genes for GO and REACTOME pathway enrichment analyses and found that GO terms and signaling pathways were significant. [106], FCN1 [107], CARNS1 [108], AMH (anti-Mullerian hormone) [109], E2F1 [110], PF4 [111], RPL3L [112], TRIM72 [113], HOXB4 [114], TP73 [115], KCNH2 [116], (advanced glycosylation end-product specific receptor) [117], SMPD3 [118], TYMP (thymidine phosphorylase) [119], RIPPLY3 [120], GREM1 [121], CYP11B2 [122], MYLK2 [123], WNT3A [124], MSX1 [125], COMP (cartilage oligomeric matrix protein) [126], FLI1 [127], ACTA1 [128], TCAP (titincap) [129], TUBB1 [130], TNNI3 [131], HSPB7 [132], DES (desmin) [133], RAP1B [134], TNNT1 [135], BHMT (betaine--homocysteine S-methyltransferase) [136], ANGPTL3 [137], CYP3A5 [138], KMO (kynurenine 3-monooxygenase) [139], HMGCS2 [140], AGXT2 [141], FABP1 [142], SLC22A12 [143], CUBN (cubilin) [144], MIOX (myo-inositol oxygenase) [145], FBP1 [146], ARG2 [147], FGF1 [148], CRY1 [149], PPARGC1A [150], UGT1A6 [151], ECHDC3 [152], CYP2C8 [153], ACOX2…”

Section: Discussionmentioning

confidence: 99%

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

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Acute kidney injury (AKI) is a type of renal disease occurs frequently in hospitalized patients, which may cause abnormal renal function and structure with increase in serum creatinine level with or without reduced urine output. With the incidence of AKI is increasing. However, the molecular mechanisms of AKI have not been elucidated. It is significant to further explore the molecular mechanisms of AKI. We downloaded the GSE139061 next generation sequencing (NGS) dataset from the Gene Expression Omnibus (GEO) database. Limma R bioconductor package was used to screen the differentially expressed genes (DEGs). Then, the enrichment analysis of DEGs in Gene Ontology (GO) function and REACTOME pathways was analyzed by g:Profiler. Next, the protein-protein interaction (PPI) network and modules was constructed and analyzed, and the hub genes were identified. Next, the miRNA-hub gene regulatory network and TF-hub gene regulatory network were built. We also validated the identified hub genes via receiver operating characteristic (ROC) curve analysis. Overall, 956 DEGs were identified, including 478 up regulated and 478 down regulated genes. The enrichment functions and pathways of DEGs involve primary metabolic process, small molecule metabolic process, striated muscle contraction and metabolism. Topological analysis of the PPI network and module revealed that hub genes, including PPP1CC, RPS2, MDFI, BMI1, RPL23A, VCAM1, ALB, SNCA, DPP4 and RPL26L1, might be involved in the development of AKI. miRNA-hub gene and TF-hub gene regulatory networks revealed that miRNAs and TFs including hsa-mir-510-3p, hsa-mir-6086 and mir-146a-5p, MAX and PAX2, might be involved in the development of AKI. Various known and newtherapeutic targets were obtained via network analysis. The results of the current investigation might be beneficial for the diagnosis and treatment of AKI.

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Section: Discussionmentioning

confidence: 99%

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

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“…However, where and how do changes in DNA methylation take place in non-CpG promoter sites? We reported that stimulatory signals of potassium treatment led to DNA demethylation around transcription factor binding sites and a transcription start site, where the chromatin structure was relaxed [ 39 ] ( Figure 4 ). DNA demethylation was observed during two days of potassium treatment, while the highest level of demethylation was evident by seven days.…”

Section: Epigenetic Control Of Cyp11b2mentioning

confidence: 99%

“…DNA demethylation was observed during two days of potassium treatment, while the highest level of demethylation was evident by seven days. The CYP11B2 promoter demethylation increased gene expression [ 39 ] ( Figure 5 A).…”

Section: Epigenetic Control Of Cyp11b2mentioning

confidence: 99%

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

Takeda

Demura

Kometani

et al. 2023

IJMS

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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.

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“…Figure 5 A shows the CpG sites of the CYP11B2 promoter region. Transcriptional activation by potassium gradually causes DNA demethylation around the CREB1- and NR4A-binding sites as well as a TSS over seven days, and its withdrawal reverses this process over the next seven days in H295R cells [ 62 ]. Although the CYP11B2 promoter is a non-CpG island promoter, each of the CREB1- and NR4A-binding sites (at positions −71/ −64 and positions −129/−114, respectively) contains one CpG dinucleotide, and these binding sites are crucial for the basal transcription activity.…”

Section: Contribution Of Dna Methylation To Human Cyp11b2 Transcriptionmentioning

confidence: 99%

DNA Methylation of the Angiotensinogen Gene, AGT, and the Aldosterone Synthase Gene, CYP11B2 in Cardiovascular Diseases

Takeda

Demura

Yoneda

et al. 2021

IJMS

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Angiotensinogen (AGT) and aldosterone play key roles in the regulation of blood pressure and are implicated in the pathogenesis of cardiovascular diseases. DNA methylation typically acts to repress gene transcription. The aldosterone synthase gene CYP11B2 is regulated by angiotensin II and potassium. DNA methylation negatively regulates AGT and CYP11B2 expression and dynamically changes in response to continuous promoter stimulation of each gene. High salt intake and excess circulating aldosterone cause DNA demethylation around the CCAAT-enhancer-binding-protein (CEBP) sites of the CYP11B2 promoter region, thereby converting the phenotype of AGT expression from an inactive to an active state in visceral adipose tissue and heart. A close association exists between low DNA methylation at CEBP-binding sites and increased AGT expression in salt-sensitive hypertensive rats. Salt-dependent hypertension may be partially affected by increased cardiac AGT expression. CpG dinucleotides in the CYP11B2 promoter are hypomethylated in aldosterone-producing adenomas. Methylation of recognition sequences of transcription factors, including CREB1, NGFIB (NR4A1), and NURR1 (NR4A2) diminish their DNA-binding activity. The methylated CpG-binding protein MECP2 interacts directly with the methylated CYP11B2 promoter. Low salt intake and angiotensin II infusion lead to upregulation of CYP11B2 expression and DNA hypomethylation in the adrenal gland. Treatment with the angiotensin II type 1 receptor antagonist decreases CYP11B2 expression and leads to DNA hypermethylation. A close association between low DNA methylation and increased CYP11B2 expression are seen in the hearts of patients with hypertrophic cardiomyopathy. These results indicate that epigenetic regulation of both AGT and CYP11B2 contribute to the pathogenesis of cardiovascular diseases.

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Effect of potassium on DNA methylation of aldosterone synthase gene

Abstract: Supplemental Digital Content is available in the text

Cited by 4 publications

References 25 publications

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

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

DNA Methylation of the Angiotensinogen Gene, AGT, and the Aldosterone Synthase Gene, CYP11B2 in Cardiovascular Diseases

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