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Cloning of the major histocompatibility complex class II promoter binding protein affected in a hereditary defect in class II gene regulation

Satola, S.
Kobr, M.
Reinhart, D.
Sanchez, C. H.
Published in Proceedings of the National Academy of Sciences. 1989, vol. 86, no. 11, p. 4200-4204
Abstract The regulation of major histocompatibility complex class II gene expression is directly involved in the control of normal and abnormal immune responses. In humans, HLA-DR, -DQ, and -DP class II heterodimers are encoded by a family of alpha- and beta-chain genes clustered in the major histocompatibility complex. Their expression is developmentally controlled and normally restricted to certain cell types. This control is mediated by cis-acting sequences in class II promoters and by trans-acting regulatory factors. Several nuclear proteins bind to class II promoter sequences. In a form of hereditary immunodeficiency characterized by a defect in a trans-acting regulatory factor controlling class II gene transcription, we have observed that one of these nuclear factors (RF-X) does not bind to its target sequence (the class II X box). A cDNA encoding RF-X was isolated by screening a phage expression library with an X-box binding-site probe. The recombinant protein has the binding specificity of RF-X, including a characteristic gradient of affinity for the X boxes of HLA-DR, -DP, and -DQ promoters. RF-X mRNA is present in the regulatory mutants, indicating a defect in the synthesis of a functional form of the RF-X protein.
Keywords Base SequenceCell LineCloning, MolecularDNA-Binding Proteins/ geneticsGene Expression RegulationGenes, MHC Class IIHumansImmunologic Deficiency Syndromes/ geneticsMolecular Sequence DataMultigene FamilyMutationPromoter Regions, GeneticTranscription Factors
Stable URL http://archive-ouverte.unige.ch/unige:11537
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Other version: http://www.pnas.org/content/86/11/4200.full.pdf
PMID: 2498880
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