RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency
RFXAP, a novel subunit of the RFX DNA binding complex is mutated in MHC class II deficiency
复制标题
DOI：
10.1093/emboj/16.5.1045
复制
发表时间：
1997-03-03
期刊：
影响因子：
11.4
通讯作者：
Reith, W
中科院分区：
文献类型：
--
作者：
Durand, B;Sperisen, P;Reith, W
主要组织相容性复合物II类（MHC-II）缺陷是一种基因调控疾病，为控制MHC-II基因转录的分子机制的遗传解剖提供了独特的机会。来自MHC-II缺陷患者的细胞系被分配到三个互补组（A、B和C），据信这反映了不同的必需MRC-II调节基因的存在。组B和C以及代表第四组（D）的体外产生的调节突变体的特征在于RFX结合活性的特异性缺陷，RFX是活化MHC-II启动子所必需的多聚体DNA结合复合物。RFX 5是RFX的一个亚基，最近发现在C组中存在突变。我们现在已经分离出一种新的基因，RFXAP（RFX相关蛋白），它编码RFX复合物的第二个亚基，RFXAP在6.1.6细胞系（D组）中突变，以及在MHC-II缺陷患者（DA）。这表明D组确实是第四个MHC-II缺陷互补组。通过用RFXAP转染的6.1.6和DA细胞系的互补完全恢复了体内所有内源性MHC-II基因的表达，证明RFXAP是一种新的必需MHC-II调节基因。
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.