EHMT1 蛋白与核因子-κB p50 结合并抑制基因表达。
EHMT1 protein binds to nuclear factor-κB p50 and represses gene expression.
机构信息
Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
出版信息
J Biol Chem. 2012 Sep 7;287(37):31207-17. doi: 10.1074/jbc.M112.365601. Epub 2012 Jul 16.
Abstract
Transcriptional homeostasis relies on the balance between positive and negative regulation of gene transcription. Methylation of histone H3 lysine 9 (H3K9) is commonly correlated with gene repression. Here, we report that a euchromatic H3K9 methyltransferase, EHMT1, functions as a negative regulator in both the NF-κB- and type I interferon-mediated gene induction pathways. EHMT1 catalyzes H3K9 methylation at promoters of NF-κB target genes. Moreover, EHMT1 interacts with p50, and, surprisingly, p50 appears to repress the expression of type I interferon genes and genes activated by type I interferons by recruiting EHMT1 to catalyze H3K9 methylation at their promoter regions. Silencing the expression of EHMT1 by RNA interference enhances expression of a subset NF-κB-regulated genes, augments interferon production, and augments antiviral immunity.
摘要
转录稳态依赖于基因转录的正调控和负调控之间的平衡。组蛋白 H3 赖氨酸 9（H3K9）的甲基化通常与基因沉默相关。在这里，我们报告说常染色质 H3K9 甲基转移酶 EHMT1 作为 NF-κB 和 I 型干扰素介导的基因诱导途径中的负调节剂发挥作用。EHMT1 在 NF-κB 靶基因的启动子上催化 H3K9 甲基化。此外，EHMT1 与 p50 相互作用，令人惊讶的是，p50 似乎通过招募 EHMT1 在其启动子区域催化 H3K9 甲基化来抑制 I 型干扰素基因和由 I 型干扰素激活的基因的表达。通过 RNA 干扰沉默 EHMT1 的表达可增强 NF-κB 调控基因的一部分的表达，增强干扰素的产生，并增强抗病毒免疫。
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