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

被引:195
作者
Durand, B [1 ]
Sperisen, P [1 ]
Emery, P [1 ]
Barras, E [1 ]
Zufferey, M [1 ]
Mach, B [1 ]
Reith, W [1 ]
机构
[1] UNIV GENEVA, SCH MED, DEPT GENET & MICROBIOL, CH-1211 GENEVA 4, SWITZERLAND
关键词
Bare Lymphocyte Syndrome; gene expression; human disease gene; MHC class II deficiency; RFX proteins;
D O I
10.1093/emboj/16.5.1045
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 MRC-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.
引用
收藏
页码:1045 / 1055
页数:11
相关论文
共 58 条