UNIGE document Scientific Article
previous document  unige:11230  next document
add to browser collection

Functional complementation of major histocompatibility complex class II regulatory mutants by the purified X-box-binding protein RFX

Kobr, M.
Published in Molecular and Cellular Biology. 1994, vol. 14, no. 10, p. 6839-6847
Abstract Major histocompatibility complex (MHC) class II deficiency, or bare lymphocyte syndrome (BLS), is a disease of gene regulation. Patients with BLS have been classified into at least three complementation groups (A, B, and C) believed to correspond to three distinct MHC class II regulatory genes. The elucidation of the molecular basis for this disease will thus clarify the mechanisms controlling the complex regulation of MHC class II genes. Complementation groups B and C are characterized by a lack of binding of RFX, a nuclear protein that normally binds specifically to the X box cis-acting element present in the promoters of all MHC class II genes. We have now purified RFX to near homogeneity by affinity chromatography. Using an in vitro transcription system based on the HLA-DRA promoter, we show here that extracts from RFX-deficient cells from patients with BLS (BLS cells) in groups B and C, which are transcriptionally inactive in this assay, can be complemented to full transcriptional activity by the purified RFX. As expected, purified RFX also restores a completely normal pattern of X box-binding complexes in these mutant extracts. This provides the first direct functional evidence that RFX is an activator of MHC class II gene transcription and that its absence is indeed responsible for the regulatory defect in MHC class II gene expression in patients with BLS.
Keywords Base SequenceCell Nucleus/chemistry/metabolismCell-Free SystemDNA-Binding Proteins/genetics/isolation & purification/ metabolismGene Expression RegulationHLA-DR Antigens/ geneticsHumansImmunologic Deficiency Syndromes/etiology/ geneticsLymphocytes/ immunology/pathologyMolecular Sequence DataMutationPromoter Regions, Genetic/ geneticsProtein BindingSubcellular Fractions/chemistry/metabolismTranscription Factors/genetics/isolation & purification/ metabolismTranscription, Genetic
Stable URL http://archive-ouverte.unige.ch/unige:11230
Full text
Article - document accessible for UNIGE members only Limited access to UNIGE
Other version: http://mcb.asm.org/cgi/reprint/14/10/6839.pdf
PMID: 7935401
136 hits and 0 download since 2010-08-27
Export document
Format :
Citation style :