title: Differential regulation of MHCII genes by PRMT6, via an AT-hook motif of RFX5.
abstract: 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.
authors.affiliation: Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas (FORTH), Nikolaou Plastira 100, GR-70013 Heraklion, Crete, Greece; Department of Biology, University of Crete, 71409 Heraklion, Crete, Greece. Electronic address: stavride@imbb.forth.gr.
authors.forename: Phoebe
authors.initials: P
authors.lastname: Stavride
authors.forename: Panagiota
authors.initials: P
authors.lastname: Arampatzi
authors.forename: Joseph
authors.initials: J
authors.lastname: Papamatheakis
mesh_terms: D024761:AT-Hook Motifs / Q000235:genetics*; D000595:Amino Acid Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006683:HLA-DQ Antigens / Q000235:genetics / Q000378:metabolism; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
chemical_list: D004268:DNA-Binding Proteins; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D009687:Nuclear Proteins; C093524:RFX5 protein, human; D000071701:Regulatory Factor X Transcription Factors; C447833:PRMT6 protein, human; D011484:Protein-Arginine N-Methyltransferases
keywords: AT-hook; MHCII expression; MHCII transcription; PRMT6; RFX5