Henryk Dreger1, Antje Ludwig2, Andrea Weller2, Gert Baumann2, Verena Stangl2, Karl Stangl2. 1. Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charité - Universitätsmedizin Berlin, Germany; DZHK (German Center for Cardiovascular Research). Electronic address: henryk.dreger@charite.de. 2. Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charité - Universitätsmedizin Berlin, Germany; DZHK (German Center for Cardiovascular Research).
Abstract
OBJECTIVE: Cytokines strongly induce expression of the inducible nitric oxide synthase (iNOS) in rodent but not in human endothelial cells. We recently identified NOS2 as a potential target of the histone methyltransferase enhancer of zeste homolog 2 which mediates trimethylation of histone 3 at lysine 27 (H3K27me3). METHODS AND RESULTS: Compared to an unspecific IgG control, chromatin immunoprecipitation using a H3K27me3-specific antibody followed by DNA quantification by PCR showed a strong DNA enrichment - indicating that NOS2 is associated with H3K27me3 in human umbilical vein endothelial cells (HUVEC). siRNA-mediated knock down of Ezh2 diminished NOS2 DNA enrichment - suggesting that the association of NOS2 with H3K27me3 is mediated by Ezh2. Ezh2 knock down, however, was not sufficient to increase iNOS expression after stimulation of HUVEC. CONCLUSION: NOS2 is associated with Ezh2-mediated H3K27me3 in HUVEC. This might contribute to an epigenetic suppression of iNOS inducibility in human endothelial cells.
OBJECTIVE: Cytokines strongly induce expression of the inducible nitric oxide synthase (iNOS) in rodent but not in human endothelial cells. We recently identified NOS2 as a potential target of the histone methyltransferase enhancer of zeste homolog 2 which mediates trimethylation of histone 3 at lysine 27 (H3K27me3). METHODS AND RESULTS: Compared to an unspecific IgG control, chromatin immunoprecipitation using a H3K27me3-specific antibody followed by DNA quantification by PCR showed a strong DNA enrichment - indicating that NOS2 is associated with H3K27me3 in human umbilical vein endothelial cells (HUVEC). siRNA-mediated knock down of Ezh2 diminished NOS2 DNA enrichment - suggesting that the association of NOS2 with H3K27me3 is mediated by Ezh2. Ezh2 knock down, however, was not sufficient to increase iNOS expression after stimulation of HUVEC. CONCLUSION:NOS2 is associated with Ezh2-mediated H3K27me3 in HUVEC. This might contribute to an epigenetic suppression of iNOS inducibility in human endothelial cells.
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Authors: Xue-Song Zhang; Jackie Li; Kimberly A Krautkramer; Michelle Badri; Thomas Battaglia; Timothy C Borbet; Hyunwook Koh; Sandy Ng; Rachel A Sibley; Yuanyuan Li; Wimal Pathmasiri; Shawn Jindal; Robin R Shields-Cutler; Ben Hillmann; Gabriel A Al-Ghalith; Victoria E Ruiz; Alexandra Livanos; Angélique B van 't Wout; Nabeetha Nagalingam; Arlin B Rogers; Susan Jenkins Sumner; Dan Knights; John M Denu; Huilin Li; Kelly V Ruggles; Richard Bonneau; R Anthony Williamson; Marcus Rauch; Martin J Blaser Journal: Elife Date: 2018-07-25 Impact factor: 8.140