TY  - JOUR
A1  - Mudersbach, Thomas
A1  - Siuda, Daniel
A1  - Kohlstedt, Karin
A1  - Fleming, Ingrid
T1  - Epigenetic control of the angiotensin-converting enzyme in endothelial cells during inflammation
T2  - PLoS one
N2  - 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.
KW  - DNA methylation
KW  - Endothelial cells
KW  - Transcription factors
KW  - Gene expression
KW  - DNA-binding proteins
KW  - Inflammatory diseases
KW  - Macrophages
KW  - Enzyme regulation
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/50059
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-500599
SN  - 1932-6203
N1  - 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.
VL  - 14
IS  - (5): e0216218
SP  - 1
EP  - 15
PB  - PLoS
CY  - Lawrence, Kan.
ER  -