en
Scientific article
English

RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency

Published inEMBO journal, vol. 16, no. 5, p. 1045-1055
Publication date1997
Abstract

Major Histocompatibility Complex class II (MHC-II) deficiency is a disease of gene regulation that provides a unique opportunity for the genetic dissection of the molecular mechanisms controlling transcription of MHC-II genes. Cell lines from MHC-II deficiency patients have been assigned to three complementation groups (A, B and C) believed to reflect the existence of distinct essential MHC-II regulatory genes. Groups B and C, as well as an in vitro generated regulatory mutant representing a fourth group (D), are characterized by a specific defect in the binding activity of RFX, a multimeric DNA binding complex that is essential for activation of MHC-II promoters. RFX5, a subunit of RFX, was recently shown to be mutated in group C. We have now isolated a novel gene, RFXAP (RFX Associated Protein), that encodes a second subunit of the RFX complex. RFXAP is mutated in the 6.1.6 cell line (group D), as well as in an MHC-II deficiency patient (DA). This establishes that group D is indeed a fourth MHC-II deficiency complementation group. Complementation of the 6.1.6 and DA cell lines by transfection with RFXAP fully restores expression of all endogenous MHC-II genes in vivo, demonstrating that RFXAP is a novel essential MHC-II regulatory gene.

Keywords
  • Amino Acid Sequence
  • Base Sequence
  • DNA/ metabolism
  • DNA-Binding Proteins/ chemistry/ genetics/metabolism
  • Flow Cytometry
  • Gene Expression Regulation/genetics
  • Genes, MHC Class II/ genetics
  • Genetic Complementation Test
  • Humans
  • Molecular Sequence Data
  • Mutation
  • Sequence Analysis
  • Severe Combined Immunodeficiency/ genetics
  • Transcription Factors/ chemistry/ genetics/metabolism
  • Transformation, Genetic/genetics
Citation (ISO format)
DURAND, Bénédicte et al. RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency. In: EMBO journal, 1997, vol. 16, n° 5, p. 1045–1055. doi: 10.1093/emboj/16.5.1045
Main files (1)
Article
accessLevelRestricted
Identifiers
ISSN of the journal0261-4189
524views
0downloads

Technical informations

Creation08/27/2010 1:34:23 PM
First validation08/27/2010 1:34:23 PM
Update time03/14/2023 4:03:09 PM
Status update03/14/2023 4:03:09 PM
Last indexation02/12/2024 7:16:29 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack