Differential regulation of MHCII genes by PRMT6, via an AT-hook motif of RFX5

• Published in: Molecular immunology 2013-12, Vol.56 (4), p.390-398
• Main Authors: Stavride, Phoebe, Arampatzi, Panagiota, Papamatheakis, Joseph
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; AT-hook; AT-Hook Motifs - genetics; Blotting, Western; Cell Line, Tumor; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Gene Expression Profiling; Gene Expression Regulation; Histocompatibility Antigens Class II - genetics; Histocompatibility Antigens Class II - metabolism; HLA-DQ Antigens - genetics; HLA-DQ Antigens - metabolism; HLA-DR Antigens - genetics; HLA-DR Antigens - metabolism; Humans; MHCII expression; MHCII transcription; Molecular Sequence Data; Mutation; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; PRMT6; Promoter Regions, Genetic - genetics; Protein Binding; Protein-Arginine N-Methyltransferases - genetics; Protein-Arginine N-Methyltransferases - metabolism; Regulatory Factor X Transcription Factors; Reverse Transcriptase Polymerase Chain Reaction; RFX5; Sequence Homology, Amino Acid
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2013.05.235

•An evolutionarily conserved AT-hook motif is present in the MHCII regulator RFX5.•The AT-hook motif is necessary for proper HLA-DQ, but not HLA-DR expression.•Defective expression of HLA-DQ is due to defective transcription of the HLA-DQA chain.•PRMT6 methylates the AT-hook and downregulates HLA-DQ expression. Major histocompatibility complexes class II are responsible for the antigen presentation that shapes the repertoire of the adaptive immune responses. All members of the MHCII family of genes are controlled by the same set of conserved transcription factors and promoter elements, resulting in coordinated transcription. We report the role of a previously unidentified AT-hook motif of the MHCII regulatory factor RFX5, and show that this is involved in regulating the transcription of the HLA-DQ, but not HLA-DR, MHCII isotype. Furthermore, PRMT6, an arginine methyltransferase known to methylate AT-hook motifs, downregulates the expression of HLA-DQ, but not HLA-DR, in an AT-hook-dependent manner. This can provide a fine-tuning mechanism for isotype-specific transcriptional regulation, where a post-translational modification modulates the relative levels of the MHCII isotypes.