Epigenetic control of the angiotensin-converting enzyme in endothelial cells during inflammation

  • The angiotensin-converting enzyme (ACE) plays a central role in the renin-angiotensin system, which is involved in the regulation of blood pressure. Alterations in ACE expression or activity are associated with various pathological phenotypes, particularly cardiovascular diseases. In human endothelial cells, ACE was shown to be negatively regulated by tumor necrosis factor (TNF) α. To examine, whether or not, epigenetic factors were involved in ACE expression regulation, methylated DNA immunoprecipitation and RNA interference experiments directed against regulators of DNA methylation homeostasis i.e., DNA methyltransferases (DNMTs) and ten-eleven translocation methylcytosine dioxygenases (TETs), were performed. TNFα stimulation enhanced DNA methylation in two distinct regions within the ACE promoter via a mechanism linked to DNMT3a and DNMT3b, but not to DNMT1. At the same time, TET1 protein expression was downregulated. In addition, DNA methylation decreased the binding affinity of the transcription factor MYC associated factor X to the ACE promoter. In conclusion, DNA methylation determines the TNFα-dependent regulation of ACE gene transcription and thus protein expression in human endothelial cells.
Author:Thomas Mudersbach, Daniel Siuda, Karin Kohlstedt, Ingrid FlemingORCiD
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/31042763
Parent Title (English):PLoS one
Place of publication:Lawrence, Kan.
Contributor(s):Osman El-Maarri
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/05/01
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/05/02
Tag:DNA methylation; DNA-binding proteins; Endothelial cells; Enzyme regulation; Gene expression; Inflammatory diseases; Macrophages; Transcription factors
Issue:(5): e0216218
Page Number:15
First Page:1
Last Page:15
Copyright: © 2019 Mudersbach et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Institutes:Medizin / Medizin
Wissenschaftliche Zentren und koordinierte Programme / Sonderforschungsbereiche / Forschungskollegs
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0