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Scientific article
English

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

Contributors

Durand, Bénédicte; Kobr, M.; Reith, Walter; Mach, Bernard

Published in

Molecular and cellular biology, vol. 14, no. 10, p. 6839-6847

Publication date

1994

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 Sequence
  • Cell Nucleus/chemistry/metabolism
  • Cell-Free System
  • DNA-Binding Proteins/genetics/isolation & purification/ metabolism
  • Gene Expression Regulation
  • HLA-DR Antigens/ genetics
  • Humans
  • Immunologic Deficiency Syndromes/etiology/ genetics
  • Lymphocytes/ immunology/pathology
  • Molecular Sequence Data
  • Mutation
  • Promoter Regions, Genetic/ genetics
  • Protein Binding
  • Subcellular Fractions/chemistry/metabolism
  • Transcription Factors/genetics/isolation & purification/ metabolism
  • Transcription, Genetic

UNIGE affiliation entities

Citation (ISO format)

DURAND, Bénédicte et al. Functional complementation of major histocompatibility complex class II regulatory mutants by the purified X-box-binding protein RFX. In: Molecular and cellular biology, 1994, vol. 14, n° 10, p. 6839–6847. doi: 10.1128/mcb.14.10.6839

Main files (1)

Article

Identifiers

Additional URL for this publication

http://mcb.asm.org/cgi/reprint/14/10/6839.pdf

Journal ISSN

0270-7306
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Technical informations

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27/08/2010 13:34:23

First validation

27/08/2010 13:34:23

Update

14/03/2023 16:03:08

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14/03/2023 16:03:08

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