{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T16:01:55Z","timestamp":1791820915389,"version":"4.3.4"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,5,15]]},"abstract":"\n Background<\/jats:title>\n \n DNA<\/jats:styled-content>\n 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\n DNA<\/jats:styled-content>\n methylation status around transcription factor binding sites and a transcription start site and activate expression of the aldosterone synthase gene (\n \n CYP<\/jats:styled-content>\n 11B2\n <\/jats:italic>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n DNA<\/jats:styled-content>\n methylation of\n \n CYP<\/jats:styled-content>\n 11B2\n <\/jats:italic>\n was analyzed in aldosterone\u2010producing adenomas, nonfunctioning adrenal adenomas, and adrenal glands and compared with the gene expression levels. CpG dinucleotides in the\n \n CYP<\/jats:styled-content>\n 11B2\n <\/jats:italic>\n promoter were found to be hypormethylated in tissues with high expression, but not in those with low expression, of\n \n CYP<\/jats:styled-content>\n 11B2\n <\/jats:italic>\n . Methylation of the\n \n CYP<\/jats:styled-content>\n 11B2\n <\/jats:italic>\n promoter fused to a reporter gene decreased transcriptional activity. Methylation of recognition sequences of transcription factors, including\n CREB<\/jats:styled-content>\n 1,\n NGFIB<\/jats:styled-content>\n (\n NR<\/jats:styled-content>\n 4A1), and\n NURR<\/jats:styled-content>\n 1 (\n NR<\/jats:styled-content>\n 4A2) diminished their\n DNA<\/jats:styled-content>\n \u2010binding activity. A methylated\u2010CpG\u2010binding protein\n MECP<\/jats:styled-content>\n 2 interacted directly with the methylated\n CYP<\/jats:styled-content>\n 11B2 promoter. In rats, low salt intake led to upregulation of\n \n CYP<\/jats:styled-content>\n 11B2\n <\/jats:italic>\n expression and\n DNA<\/jats:styled-content>\n hypomethylation in the adrenal gland. Treatment with angiotensin\n II<\/jats:styled-content>\n type 1 receptor antagonist decreased\n \n CYP<\/jats:styled-content>\n 11B2\n <\/jats:italic>\n expression and led to\n DNA<\/jats:styled-content>\n hypermethylation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n DNA<\/jats:styled-content>\n demethylation may switch the phenotype of\n \n CYP<\/jats:styled-content>\n 11B2\n <\/jats:italic>\n expression from an inactive to an active state and regulate aldosterone biosynthesis.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.117.008281","type":"journal-article","created":{"date-parts":[[2018,5,8]],"date-time":"2018-05-08T09:20:09Z","timestamp":1525771209000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Epigenetic Regulation of Aldosterone Synthase Gene by Sodium and Angiotensin II"],"prefix":"10.1161","volume":"7","author":[{"given":"Yoshimichi","family":"Takeda","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Demura","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Kanazawa University School of Medicine, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigehiro","family":"Karashima","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Yoneda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Kometani","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Aono","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin\u2010ichi","family":"Horike","sequence":"additional","affiliation":[{"name":"Division of Functional Genomics, Kanazawa University Advanced Science Research Center, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makiko","family":"Meguro\u2010Horike","sequence":"additional","affiliation":[{"name":"Division of Functional Genomics, Kanazawa University Advanced Science Research Center, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyu","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kanazawa University School of Medicine, Kanazawa, Japan"},{"name":"Innovative Clinical Research Center, Kanazawa University, Kanazawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2003-0005"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0069"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1081\/ERC-200044042"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-0667"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.11.6538"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0011982"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08456"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ11-0133"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.36.4.495"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-021527"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.11.5.9920"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2005.07.021"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2007.12.003"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-3495"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.116.08313"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-3285"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0109"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1999"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.03.027"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.02303"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/hc0602.104675"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-014-2295-9"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000258855.60637.58"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.117.008281","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:14:15Z","timestamp":1715598855000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.117.008281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,5,15]]},"references-count":23,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2018,5,15]]}},"alternative-id":["10.1161\/JAHA.117.008281"],"URL":"https:\/\/doi.org\/10.1161\/jaha.117.008281","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,5,15]]},"assertion":[{"value":"2017-12-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e008281"}}