TY  - JOUR
A1  - Fork, Christian
A1  - Vasconez, Andrea E.
A1  - Janetzko, Patrick
A1  - Angioni, Carlo
A1  - Schreiber, Yannick
A1  - Ferreirós Bouzas, Nerea
A1  - Geisslinger, Gerd
A1  - Leisegang, Matthias
A1  - Steinhilber, Dieter
A1  - Brandes, Ralf
T1  - Epigenetic control of microsomal prostaglandin E synthase-1 by HDAC-mediated recruitment of p300
T2  - Journal of lipid research
N2  - Nonsteroidal anti-inflammatory drugs are the most widely used medicine to treat pain and inflammation, and to inhibit platelet function. Understanding the expression regulation of enzymes of the prostanoid pathway is of great medical relevance. Histone acetylation crucially controls gene expression. We set out to identify the impact of histone deacetylases (HDACs) on the generation of prostanoids and examine the consequences on vascular function. HDAC inhibition (HDACi) with the pan-HDAC inhibitor, vorinostat, attenuated prostaglandin (PG)E2 generation in the murine vasculature and in human vascular smooth muscle cells. In line with this, the expression of the key enzyme for PGE2 synthesis, microsomal PGE synthase-1 (PTGES1), was reduced by HDACi. Accordingly, the relaxation to arachidonic acid was decreased after ex vivo incubation of murine vessels with HDACi. To identify the underlying mechanism, chromatin immunoprecipitation (ChIP) and ChIP-sequencing analysis were performed. These results suggest that HDACs are involved in the recruitment of the transcriptional activator p300 to the PTGES1 gene and that HDACi prevented this effect. In line with the acetyltransferase activity of p300, H3K27 acetylation was reduced after HDACi and resulted in the formation of heterochromatin in the PTGES1 gene. In conclusion, HDAC activity maintains PTGES1 expression by recruiting p300 to its gene.
KW  - epigenetics
KW  - prostaglandins
KW  - prostaglandin E
KW  - vascular biology
KW  - smooth muscle cells
KW  - histone deacetylase
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/77318
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-773181
SN  - 0022-2275
VL  - 58.2017
IS  - 2
SP  - 386
EP  - 392
PB  - American Society for Biochemistry and Molecular Biology Publications
CY  - Bethesda, Md
ER  -