Epigenetic Regulation of Aldosterone Synthase Gene by Sodium and Angiotensin <styled-content style="fixed-case">II</styled-content>

BackgroundDNA methylation is believed to be maintained in adult somatic cells. Recent findings, however, suggest that all methylation patterns are not stable. We demonstrate that stimulatory signals can change the DNA methylation status around transcription factor binding sites and a transcription s...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Yoshimichi Takeda, Masashi Demura, Fen Wang, Shigehiro Karashima, Takashi Yoneda, Mitsuhiro Kometani, Atsushi Hashimoto, Daisuke Aono, Shin‐ichi Horike, Makiko Meguro‐Horike, Masakazu Yamagishi, Yoshiyu Takeda
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2018
Materias:	aldosterone angiotensin II CYP11B2 epigenetics sodium Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/cafd199cef5c470fb67f4cd043f28428
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:cafd199cef5c470fb67f4cd043f28428
record_format	dspace
spelling	oai:doaj.org-article:cafd199cef5c470fb67f4cd043f284282021-11-12T17:01:48ZEpigenetic Regulation of Aldosterone Synthase Gene by Sodium and Angiotensin <styled-content style="fixed-case">II</styled-content>10.1161/JAHA.117.0082812047-9980https://doaj.org/article/cafd199cef5c470fb67f4cd043f284282018-05-01T00:00:00Zhttps://www.ahajournals.org/doi/10.1161/JAHA.117.008281https://doaj.org/toc/2047-9980BackgroundDNA methylation is believed to be maintained in adult somatic cells. Recent findings, however, suggest that all methylation patterns are not stable. We demonstrate that stimulatory signals can change the DNA methylation status around transcription factor binding sites and a transcription start site and activate expression of the aldosterone synthase gene (CYP11B2). Methods and ResultsDNA methylation of CYP11B2 was analyzed in aldosterone‐producing adenomas, nonfunctioning adrenal adenomas, and adrenal glands and compared with the gene expression levels. CpG dinucleotides in the CYP11B2 promoter were found to be hypormethylated in tissues with high expression, but not in those with low expression, of CYP11B2. Methylation of the 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. In rats, low salt intake led to upregulation of CYP11B2 expression and DNA hypomethylation in the adrenal gland. Treatment with angiotensin II type 1 receptor antagonist decreased CYP11B2 expression and led to DNA hypermethylation. ConclusionsDNA demethylation may switch the phenotype of CYP11B2 expression from an inactive to an active state and regulate aldosterone biosynthesis.Yoshimichi TakedaMasashi DemuraFen WangShigehiro KarashimaTakashi YonedaMitsuhiro KometaniAtsushi HashimotoDaisuke AonoShin‐ichi HorikeMakiko Meguro‐HorikeMasakazu YamagishiYoshiyu TakedaWileyarticlealdosteroneangiotensin IICYP11B2epigeneticssodiumDiseases of the circulatory (Cardiovascular) systemRC666-701ENJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 7, Iss 10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	aldosterone angiotensin II CYP11B2 epigenetics sodium Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	aldosterone angiotensin II CYP11B2 epigenetics sodium Diseases of the circulatory (Cardiovascular) system RC666-701 Yoshimichi Takeda Masashi Demura Fen Wang Shigehiro Karashima Takashi Yoneda Mitsuhiro Kometani Atsushi Hashimoto Daisuke Aono Shin‐ichi Horike Makiko Meguro‐Horike Masakazu Yamagishi Yoshiyu Takeda Epigenetic Regulation of Aldosterone Synthase Gene by Sodium and Angiotensin <styled-content style="fixed-case">II</styled-content>
description	BackgroundDNA methylation is believed to be maintained in adult somatic cells. Recent findings, however, suggest that all methylation patterns are not stable. We demonstrate that stimulatory signals can change the DNA methylation status around transcription factor binding sites and a transcription start site and activate expression of the aldosterone synthase gene (CYP11B2). Methods and ResultsDNA methylation of CYP11B2 was analyzed in aldosterone‐producing adenomas, nonfunctioning adrenal adenomas, and adrenal glands and compared with the gene expression levels. CpG dinucleotides in the CYP11B2 promoter were found to be hypormethylated in tissues with high expression, but not in those with low expression, of CYP11B2. Methylation of the 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. In rats, low salt intake led to upregulation of CYP11B2 expression and DNA hypomethylation in the adrenal gland. Treatment with angiotensin II type 1 receptor antagonist decreased CYP11B2 expression and led to DNA hypermethylation. ConclusionsDNA demethylation may switch the phenotype of CYP11B2 expression from an inactive to an active state and regulate aldosterone biosynthesis.
format	article
author	Yoshimichi Takeda Masashi Demura Fen Wang Shigehiro Karashima Takashi Yoneda Mitsuhiro Kometani Atsushi Hashimoto Daisuke Aono Shin‐ichi Horike Makiko Meguro‐Horike Masakazu Yamagishi Yoshiyu Takeda
author_facet	Yoshimichi Takeda Masashi Demura Fen Wang Shigehiro Karashima Takashi Yoneda Mitsuhiro Kometani Atsushi Hashimoto Daisuke Aono Shin‐ichi Horike Makiko Meguro‐Horike Masakazu Yamagishi Yoshiyu Takeda
author_sort	Yoshimichi Takeda
title	Epigenetic Regulation of Aldosterone Synthase Gene by Sodium and Angiotensin <styled-content style="fixed-case">II</styled-content>
title_short	Epigenetic Regulation of Aldosterone Synthase Gene by Sodium and Angiotensin <styled-content style="fixed-case">II</styled-content>
title_full	Epigenetic Regulation of Aldosterone Synthase Gene by Sodium and Angiotensin <styled-content style="fixed-case">II</styled-content>
title_fullStr	Epigenetic Regulation of Aldosterone Synthase Gene by Sodium and Angiotensin <styled-content style="fixed-case">II</styled-content>
title_full_unstemmed	Epigenetic Regulation of Aldosterone Synthase Gene by Sodium and Angiotensin <styled-content style="fixed-case">II</styled-content>
title_sort	epigenetic regulation of aldosterone synthase gene by sodium and angiotensin <styled-content style="fixed-case">ii</styled-content>
publisher	Wiley
publishDate	2018
url	https://doaj.org/article/cafd199cef5c470fb67f4cd043f28428
work_keys_str_mv	AT yoshimichitakeda epigeneticregulationofaldosteronesynthasegenebysodiumandangiotensinstyledcontentstylefixedcaseiistyledcontent AT masashidemura epigeneticregulationofaldosteronesynthasegenebysodiumandangiotensinstyledcontentstylefixedcaseiistyledcontent AT fenwang epigeneticregulationofaldosteronesynthasegenebysodiumandangiotensinstyledcontentstylefixedcaseiistyledcontent AT shigehirokarashima epigeneticregulationofaldosteronesynthasegenebysodiumandangiotensinstyledcontentstylefixedcaseiistyledcontent AT takashiyoneda epigeneticregulationofaldosteronesynthasegenebysodiumandangiotensinstyledcontentstylefixedcaseiistyledcontent AT mitsuhirokometani epigeneticregulationofaldosteronesynthasegenebysodiumandangiotensinstyledcontentstylefixedcaseiistyledcontent AT atsushihashimoto epigeneticregulationofaldosteronesynthasegenebysodiumandangiotensinstyledcontentstylefixedcaseiistyledcontent AT daisukeaono epigeneticregulationofaldosteronesynthasegenebysodiumandangiotensinstyledcontentstylefixedcaseiistyledcontent AT shinichihorike epigeneticregulationofaldosteronesynthasegenebysodiumandangiotensinstyledcontentstylefixedcaseiistyledcontent AT makikomegurohorike epigeneticregulationofaldosteronesynthasegenebysodiumandangiotensinstyledcontentstylefixedcaseiistyledcontent AT masakazuyamagishi epigeneticregulationofaldosteronesynthasegenebysodiumandangiotensinstyledcontentstylefixedcaseiistyledcontent AT yoshiyutakeda epigeneticregulationofaldosteronesynthasegenebysodiumandangiotensinstyledcontentstylefixedcaseiistyledcontent
_version_	1718430398349836288

Epigenetic Regulation of Aldosterone Synthase Gene by Sodium and Angiotensin <styled-content style="fixed-case">II</styled-content>

Ejemplares similares