Associations and interactions between bare lymphocyte syndrome factors

Mol Cell Biol. 2000 Sep;20(17):6587-99. doi: 10.1128/MCB.20.17.6587-6599.2000.


The bare lymphocyte syndrome, a severe combined immunodeficiency due to loss of major histocompatibility complex (MHC) class II gene expression, is caused by inherited mutations in the genes encoding the heterotrimeric transcription factor RFX (RFX-B, RFX5, and RFXAP) and the class II transactivator CIITA. Mutagenesis of the RFX genes was performed, and the properties of the proteins were analyzed with regard to transactivation, DNA binding, and protein-protein interactions. The results identified specific domains within each of the three RFX subunits that were necessary for RFX complex formation, including the ankyrin repeats of RFX-B. DNA binding was dependent on RFX complex formation, and transactivation was dependent on a region of RFX5. RFX5 was found to interact with CIITA, and this interaction was dependent on a proline-rich domain within RFX5. Thus, these studies have defined the protein domains required for the functional regulation of MHC class II genes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Ankyrins / metabolism
  • COS Cells
  • Cell Line
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Flow Cytometry
  • Genes, MHC Class II / genetics
  • Genes, Reporter
  • Glutathione Transferase / metabolism
  • Humans
  • Mutagenesis
  • Nuclear Proteins*
  • Plasmids / metabolism
  • Precipitin Tests
  • Proline / metabolism
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / metabolism
  • Regulatory Factor X Transcription Factors
  • Severe Combined Immunodeficiency / genetics*
  • Severe Combined Immunodeficiency / metabolism*
  • Trans-Activators / chemistry
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Transfection


  • Ankyrins
  • DNA-Binding Proteins
  • MHC class II transactivator protein
  • Nuclear Proteins
  • RFX5 protein, human
  • RFXANK protein, human
  • RFXAP protein, human
  • Recombinant Fusion Proteins
  • Regulatory Factor X Transcription Factors
  • Trans-Activators
  • Transcription Factors
  • DNA
  • Proline
  • Glutathione Transferase