title: Dynamic CCAAT/enhancer binding protein-associated changes of DNA methylation in the angiotensinogen gene.
abstract: DNA methylation patterns are maintained in adult somatic cells. Recent findings, however, suggest that all methylation patterns are not preserved. We demonstrate that stimulatory signals can change the DNA methylation status at a CCAAT/enhancer binding protein (CEBP) binding site and a transcription start site and activate expression of the angiotensinogen gene (AGT). A CEBP binding site in the human AGT promoter was hypomethylated in tissues with high expression of AGT, but not in those with low expression. The transcriptional activity of AGT promoter sequences cloned into a reporter plasmid depended on DNA methylation. In cultured human cells, interleukin 6 stimulation caused DNA demethylation around a CEBP binding site and a transcription start site; demethylation was accompanied by increased CEBP-β recruitment and chromatin accessibility of the AGT promoter. DNA methylation activity decreased in the nucleus. Excess circulating aldosterone upregulated AGT expression and was accompanied by DNA hypomethylation around a CEBP binding site and a transcription start site in human visceral adipose tissue. High salt intake led to upregulation of Agt expression, DNA hypomethylation around 2 CEBP binding sites and a transcription start site, and decreased DNA methylation activity in rat visceral adipose tissue. Taken together, CEBP binding initiates chromatin relaxation and transcription, which are followed by DNA demethylation around a CEBP binding site and a transcription start site in the AGT promoter. Decreased DNA methylation activity in the nucleus may play a role in DNA demethylation. DNA demethylation switches the phenotype of AGT expression from an inactive to an active state.
authors.affiliation: Department of Hygiene, Kanazawa University School of Medicine, 13-1 Takara-machi, Kanazawa 920-8640, Japan. m-demura@med.kanazawa-u.ac.jp.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.forename: Masashi
authors.initials: M
authors.lastname: Demura
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Aoshuang
authors.initials: A
authors.lastname: Zhu
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Karashima
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoneda
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Demura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Maeda
authors.forename: Mikio
authors.initials: M
authors.lastname: Namiki
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Ono
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Akagi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamagishi
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Saijoh
authors.forename: Yoshiyu
authors.initials: Y
authors.lastname: Takeda
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000502:physiology*; D000328:Adult; D000808:Angiotensinogen / Q000235:genetics*; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D019175:DNA Methylation / Q000187:drug effects / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D051381:Rats; D024363:Transcription Initiation Site / Q000502:physiology
chemical_list: C534931:AGT protein, human; C534933:Agt protein, rat; D022782:CCAAT-Enhancer-Binding Protein-beta; C545012:CEBPB protein, human; C545014:Cebpb protein, rat; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D000808:Angiotensinogen
keywords: CCAAT-enhancer binding protein-β; CEBPB protein, human; DNA methylation; angiotensinogen; chromatin; transcription initiation site