Journal
BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
Volume 1859, Issue 5, Pages 687-696Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagrm.2016.03.004
Keywords
Transcriptional regulation; Epigenetics; PRMT5; CIITA; MHC 11; Macrophage
Categories
Funding
- Natural Science Foundation of China [31270805, 31200645]
- Ministry of Education [20123234110008]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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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-gamma) and mediated by class II transactivator (CIITA). The underlying epigenetic mechanism, however, is not completely understood. Here we report that following IFN-gamma stimulation, symmetrically dimethylated histone H3 arginine 2 (H3R2Me2s) accumulated on the MHC II promoter along with CIITA. IFN-gamma augmented expression, nuclear translocation, and promoter binding of the protein arginine methyltransferase PRMT5 in macrophages. Over-expression of PRMT5 potentiated IFN-gamma 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-gamma. 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-gamma. Taken together, our data reveal a pathophysiologically relevant role for PRMT5 in MHC II transactivation in macrophages. (C) 2016 Elsevier B.V. All rights reserved.
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