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Biochim Biophys Acta. 2016 May;1859(5):687-96. doi: 10.1016/j.bbagrm.2016.03.004. Epub 2016 Mar 10.

The arginine methyltransferase PRMT5 regulates CIITA-dependent MHC II transcription.

Author information

1
Key Laboratory of Cardiovascular Disease, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.
2
Key Laboratory of Cardiovascular Disease, Department of Pathophysiology, Nanjing Medical University, Nanjing, China; Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
3
Department of Respiratory Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, China.
4
Key Laboratory of Cardiovascular Disease, Department of Pathophysiology, Nanjing Medical University, Nanjing, China; Department of Nursing, Jiangsu Jiankang Vocational University, Nanjing, China.
5
Key Laboratory of Cardiovascular Disease, Department of Pathophysiology, Nanjing Medical University, Nanjing, China. Electronic address: yxu2005@gmail.com.

Abstract

Class II major histocompatibility complex (MHC II) dependent antigen presentation serves as a key step in mammalian adaptive immunity and host defense. In antigen presenting cells (e.g., macrophages), MHC II transcription can be activated by interferon gamma (IFN-γ) and mediated by class II transactivator (CIITA). The underlying epigenetic mechanism, however, is not completely understood. Here we report that following IFN-γ stimulation, symmetrically dimethylated histone H3 arginine 2 (H3R2Me2s) accumulated on the MHC II promoter along with CIITA. IFN-γ augmented expression, nuclear translocation, and promoter binding of the protein arginine methyltransferase PRMT5 in macrophages. Over-expression of PRMT5 potentiated IFN-γ induced activation of MHC II transcription in an enzyme activity-dependent manner. In contrast, PRMT5 silencing or inhibition of PRMT5 activity by methylthioadenosine (MTA) suppressed MHC II transactivation by IFN-γ. CIITA interacted with and recruited PRMT5 to the MHC II promoter and mediated the synergy between PRMT5 and ASH2/WDR5 to activate MHC II transcription. PRMT5 expression was down-regulated in senescent and H2O2-treated macrophages rendering ineffectual induction of MHC II transcription by IFN-γ. Taken together, our data reveal a pathophysiologically relevant role for PRMT5 in MHC II transactivation in macrophages.

KEYWORDS:

CIITA; Epigenetics; MHC II; Macrophage; PRMT5; Transcriptional regulation

PMID:
26972221
DOI:
10.1016/j.bbagrm.2016.03.004
[Indexed for MEDLINE]

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