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

Durand, Bénédicte; Sperisen, P.; Emery, P.; Barras, Emmanuele; Zufferey, Madeleine; Mach, Bernard; Reith, Walter

doi:10.1093/emboj/16.5.1045

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Title		RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency
Authors		Durand, Bénédicte Sperisen, P. Emery, P. Barras, Emmanuele Zufferey, Madeleine Mach, Bernard Reith, Walter
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 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
Identifiers		DOI: 10.1093/emboj/16.5.1045 PMID: 9118943
Full text		Article - Limited access to UNIGE Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1169704/pdf/001045.pdf
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie
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 https://archive-ouverte.unige.ch/unige:11231