title: Epigenetic suppression of iNOS expression in human endothelial cells: A potential role of Ezh2-mediated H3K27me3.
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).
  
  
  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.
  
  
  CONCLUSIONS
  NOS2 is associated with Ezh2-mediated H3K27me3 in HUVEC. This might contribute to an epigenetic suppression of iNOS inducibility in human endothelial cells.
authors: Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charité - Universitätsmedizin Berlin, Germany; DZHK (German Center for Cardiovascular Research). Electronic address: henryk.dreger@charite.de.
authors: Henryk
authors: H
authors: Dreger
authors: Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charité - Universitätsmedizin Berlin, Germany; DZHK (German Center for Cardiovascular Research).
authors: Antje
authors: A
authors: Ludwig
authors: Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charité - Universitätsmedizin Berlin, Germany; DZHK (German Center for Cardiovascular Research).
authors: Andrea
authors: A
authors: Weller
authors: Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charité - Universitätsmedizin Berlin, Germany; DZHK (German Center for Cardiovascular Research).
authors: Gert
authors: G
authors: Baumann
authors: Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charité - Universitätsmedizin Berlin, Germany; DZHK (German Center for Cardiovascular Research).
authors: Verena
authors: V
authors: Stangl
authors: Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charité - Universitätsmedizin Berlin, Germany; DZHK (German Center for Cardiovascular Research).
authors: Karl
authors: K
authors: Stangl
mesh_terms: D002478:Cells, Cultured; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D055785:Gene Knockdown Techniques; D006657:Histones / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering
chemical_list: D006657:Histones; D034741:RNA, Small Interfering; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
keywords: Endothelial cells; Enhancer of zeste homolog 2; Epigenetic regulation; H3K27me3; Nitric oxide synthase