Scientific article

A gene encoding a novel RFX-associated transactivator is mutated in the majority of MHC class II deficiency patients

Published inNature genetics, vol. 20, no. 3, p. 273-277
Publication date1998

Major histocompatibility class II (MHC-II) molecules are transmembrane proteins that have a central role in development and control of the immune system. They are encoded by a multigene family and their expression is tightly regulated. MHC-II deficiency (OMIM 209920) is an autosomal recessive immunodeficiency syndrome resulting from defects in trans-acting factors essential for transcription of MHC-II genes. There are four genetic complementation groups (A, B, C and D), reflecting the existence of four MHC-II regulators. The factors defective in groups A (CIITA), C (RFX5) and D (RFXAP) have been identified. CIITA is a non-DNA-binding co-activator that controls the cell-type specificity and inducibility of MHC-II expression. RFX5 and RFXAP are two subunits of RFX, a multi-protein complex that binds the X box motif of MHC-II promoters. Mutations in the genes encoding RFX5 (RFX5) or RFXAP (RFXAP) abolish binding of RFX (refs 7,8,12). Similar to groups C and D, group B is characterized by a defect in RFX binding, and although it accounts for the majority of patients, the factor defective in group B has remained unknown. We report here the isolation of RFX by a novel single-step DNA-affinity purification approach and the identification of RFXANK, the gene encoding a third subunit of RFX. RFXANK restores MHC-II expression in cell lines from patients in group B and is mutated in these patients. RFXANK contains a protein-protein interaction region consisting of three ankyrin repeats. Its interaction with RFX5 and RFXAP is essential for binding of the RFX complex to MHC-II promoters.

  • Amino Acid Sequence
  • Base Sequence
  • DNA, Complementary/genetics
  • DNA-Binding Proteins/chemistry/ genetics/metabolism
  • Female
  • Genes, MHC Class II
  • Histocompatibility Antigens Class II/ metabolism
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation
  • Pedigree
  • Promoter Regions, Genetic
  • Sequence Homology, Amino Acid
  • Trans-Activators/chemistry/ genetics/metabolism
  • Transcription Factors/chemistry/ genetics/metabolism
Citation (ISO format)
MASTERNAK, Krzysztof et al. A gene encoding a novel RFX-associated transactivator is mutated in the majority of MHC class II deficiency patients. In: Nature genetics, 1998, vol. 20, n° 3, p. 273–277. doi: 10.1038/3081
Main files (1)
ISSN of the journal1061-4036

Technical informations

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