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RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency
Author(s) -
Durand Bénédicte,
Sperisen Peter,
Emery Patrick,
Barras Emmanuèle,
Zufferey Madeleine,
Mach Bernard,
Reith Walter
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.5.1045
Subject(s) - biology , protein subunit , genetics , dna , mhc class ii , major histocompatibility complex , computational biology , gene
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.