title: Cloning of the major histocompatibility complex class II promoter binding protein affected in a hereditary defect in class II gene regulation.
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.
authors.affiliation: Department of Microbiology, University of Geneva Medical School, Switzerland.
authors.forename: W
authors.initials: W
authors.lastname: Reith
authors.forename: E
authors.initials: E
authors.lastname: Barras
authors.forename: S
authors.initials: S
authors.lastname: Satola
authors.forename: M
authors.initials: M
authors.lastname: Kobr
authors.forename: D
authors.initials: D
authors.lastname: Reinhart
authors.forename: C H
authors.initials: CH
authors.lastname: Sanchez
authors.forename: B
authors.initials: B
authors.lastname: Mach
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D005802:Genes, MHC Class II; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D009154:Mutation; D011401:Promoter Regions, Genetic; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors
chemical_list: D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors