Protein arginine methyltransferase 1 (PRMT1) represses MHC II transcription in macrophages by methylating CIITA.
Protein arginine methyltransferase 1 (PRMT1) represses MHC II transcription in macrophages by methylating CIITA.
复制标题
蛋白精氨酸甲基转移酶 1 (PRMT1) 通过甲基化 CIITA 抑制巨噬细胞中 MHC II 转录
DOI：
10.1038/srep40531
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发表时间：
2017-01-17
影响因子：
4.6
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Fan Z;Li J;Li P;Ye Q;Xu H;Wu X;Xu Y
外源抗原的有效呈递触发T淋巴细胞的活化和对入侵病原体的强大宿主防御。这种病理生理过程依赖于抗原呈递细胞如巨噬细胞中主要组织相容性复合体（MHC）分子的表达。异常的MHC II反式激活在动脉粥样硬化的发病机制中起着至关重要的作用。II类反式激活因子（CIITA）介导干扰素γ（IFN-γ）对MHC II的诱导。CIITA的活性可以在翻译后水平进行微调，但其机制尚未得到充分认识。我们研究了蛋白质精氨酸甲基转移酶1（PRMT 1）在这一过程中的作用。我们在这里报告CIITA与PRMT 1相互作用。IFN-γ处理下调PRMT 1表达并减弱PRMT 1与MHC II启动子的结合。PRMT 1的过度表达抑制了MHC II启动子的活性，而PRMT 1的缺失增强了MHC II的反式激活。在机制上，PRMT 1甲基化CIITA并促进CIITA降解。因此，我们的数据揭示了PRMT 1在抑制CIITA介导的MHC II反式激活中的先前未被认识的作用。
Efficient presentation of alien antigens triggers activation of T lymphocytes and robust host defense against invading pathogens. This pathophysiological process relies on the expression of major histocompatibility complex (MHC) molecules in antigen presenting cells such as macrophages. Aberrant MHC II transactivation plays a crucial role in the pathogenesis of atherosclerosis. Class II transactivator (CIITA) mediates MHC II induction by interferon gamma (IFN-γ). CIITA activity can be fine-tuned at the post-translational level, but the mechanisms are not fully appreciated. We investigated the role of protein arginine methyltransferase 1 (PRMT1) in this process. We report here that CIITA interacted with PRMT1. IFN-γ treatment down-regulated PRMT1 expression and attenuated PRMT1 binding on the MHC II promoter. Over-expression of PRMT1 repressed MHC II promoter activity while PRMT1 depletion enhanced MHC II transactivation. Mechanistically, PRMT1 methylated CIITA and promoted CIITA degradation. Therefore, our data reveal a previously unrecognized role for PRMT1 in suppressing CIITA-mediated MHC II transactivation.