A novel DNA-binding regulatory factor is mutated in primary MHC class II deficiency (bare lymphocyte syndrome).
Regulation of MHC class II gene expression is an essential aspect of the control of the immune response. Primary MHC class II deficiency is a genetically heterogeneous disease of gene regulation that offers the unique opportunity of a genetic approach for the identification of the functionally relevant regulatory genes and factors. Most patients exhibit a characteristic defect in the binding of a nuclear complex, RFX, to the X box motif of MHC class II promoters. Genetic complementation of a B-lymphocyte cell line from such a patient with a cDNA expression library has allowed us to isolate RFX5, the regulatory gene responsible for the MHC class II deficiency. This gene encodes a novel DNA-binding protein that is indeed a subunit of the RFX complex. Mutations in the RFX5 gene have been characterized in two patients. Transfection of the patient's cells with the RFX5 cDNA repairs the binding defect and fully restores expression of all the endogenous MHC class II genes in vivo.
Steimle
V
V
Jeantet Laboratory of Molecular Genetics, Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
Durand
B
B
Barras
E
E
Zufferey
M
M
Hadam
M R
MR
Mach
B
B
Reith
W
W
D000595:Amino Acid Sequence; D001402:B-Lymphocytes; D001483:Base Sequence; D002457:Cell Extracts; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II / Q000235:genetics*; D005809:Genes, Regulator / Q000235:genetics*; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D000071701:Regulatory Factor X Transcription Factors; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D016511:Severe Combined Immunodeficiency / Q000235:genetics*; D014162:Transfection
D002457:Cell Extracts; D004268:DNA-Binding Proteins; C093524:RFX5 protein, human; D011993:Recombinant Fusion Proteins; D000071701:Regulatory Factor X Transcription Factors; D004247:DNA