Dreger Henryk, Ludwig Antje, Weller Andrea, Baumann Gert, Stangl Verena, Stangl Karl
Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charité - Universitätsmedizin Berlin, Germany; DZHK (German Center for Cardiovascular Research).
Medizinische Klinik für Kardiologie und Angiologie, Campus Mitte, Charité - Universitätsmedizin Berlin, Germany; DZHK (German Center for Cardiovascular Research).
Genomics. 2016 Apr;107(4):145-9. doi: 10.1016/j.ygeno.2016.02.002. Epub 2016 Feb 4.
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).
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.
NOS2 is associated with Ezh2-mediated H3K27me3 in HUVEC. This might contribute to an epigenetic suppression of iNOS inducibility in human endothelial cells.
细胞因子可强烈诱导啮齿动物内皮细胞中诱导型一氧化氮合酶（iNOS）的表达，但对人内皮细胞无此作用。我们最近鉴定出一氧化氮合酶2（NOS2）是zeste同源物2组蛋白甲基转移酶增强子的潜在靶点，该增强子介导组蛋白3赖氨酸27位点的三甲基化（H3K27me3）。
与非特异性IgG对照相比，使用H3K27me3特异性抗体进行染色质免疫沉淀，随后通过PCR进行DNA定量分析，结果显示DNA大量富集，表明在人脐静脉内皮细胞（HUVEC）中，NOS2与H3K27me3相关。小干扰RNA（siRNA）介导的Ezh2基因敲低减少了NOS2的DNA富集，提示NOS2与H3K27me3的关联由Ezh2介导。然而，Ezh2基因敲低不足以在刺激HUVEC后增加iNOS的表达。
在HUVEC中，NOS2与Ezh2介导的H3K27me3相关。这可能有助于对人内皮细胞中iNOS诱导性进行表观遗传抑制。
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