title: Protein arginine methyltransferase 1 (PRMT1) represses MHC II transcription in macrophages by methylating CIITA.
abstract: 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.
authors.affiliation: Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital to Nanjing University, Nanjing, China.|Key Laboratory of Cardiovascular Disease, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Key Laboratory of Cardiovascular Disease, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Cardiovascular Disease, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.|Department of Gastroenterology, Second Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital to Nanjing University, Nanjing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Key Laboratory of Cardiovascular Disease, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Key Laboratory of Cardiovascular Disease, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Key Laboratory of Cardiovascular Disease, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism*; D008745:Methylation; D009687:Nuclear Proteins / Q000235:genetics*; D011485:Protein Binding; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism*; D059748:Proteolysis; D012097:Repressor Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D007371:Interferon-gamma; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases