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

Sperisen, P.
Emery, P.
Published in EMBO Journal. 1997, vol. 16, no. 5, p. 1045-1055
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 SequenceBase SequenceDNA/ metabolismDNA-Binding Proteins/ chemistry/ genetics/metabolismFlow CytometryGene Expression Regulation/geneticsGenes, MHC Class II/ geneticsGenetic Complementation TestHumansMolecular Sequence DataMutationSequence AnalysisSevere Combined Immunodeficiency/ geneticsTranscription Factors/ chemistry/ genetics/metabolismTransformation, Genetic/genetics
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PMID: 9118943
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