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Scientific article
English

CIITA is a transcriptional coactivator that is recruited to MHC class II promoters by multiple synergistic interactions with an enhanceosome complex

Published inGenes & development, vol. 14, no. 9, p. 1156-1166
Publication date2000
Abstract

By virtue of its control over major histocompatibility complex class II (MHC-II) gene expression, CIITA represents a key molecule in the regulation of adaptive immune responses. It was first identified as a factor that is defective in MHC-II deficiency, a hereditary disease characterized by the absence of MHC-II expression. CIITA is a highly regulated transactivator that governs all spatial, temporal, and quantitative aspects of MHC-II expression. It has been proposed to act as a non-DNA-binding transcriptional coactivator, but evidence that it actually functions at the level of MHC-II promoters was lacking. By means of chromatin immunoprecipitation assays, we show here for the first time that CIITA is physically associated with MHC-II, as well as HLA-DM, Ii, MHC-I, and beta(2)m promoters in vivo. To dissect the mechanism by which CIITA is recruited to the promoter, we have developed a DNA-dependent coimmunoprecipitation assay and a pull-down assay using immobilized promoter templates. We demonstrate that CIITA recruitment depends on multiple, synergistic protein-protein interactions with DNA-bound factors constituting the MHC-II enhanceosome. CIITA therefore represents a paradigm for a novel type of regulatory and gene-specific transcriptional cofactor.

Keywords
  • B-Lymphocytes/ immunology
  • Cell Line
  • Chromatin/physiology
  • DNA-Binding Proteins/genetics/metabolism
  • Gene Expression Regulation/ immunology
  • Genes, MHC Class II
  • HLA-D Antigens/ genetics
  • HLA-DR Antigens/genetics
  • Humans
  • Nuclear Proteins
  • Promoter Regions, Genetic
  • Recombinant Proteins/metabolism
  • Trans-Activators/ metabolism
  • Transfection
  • Tumor Cells, Cultured
Affiliation Not a UNIGE publication
Citation (ISO format)
MASTERNAK, Krzysztof et al. CIITA is a transcriptional coactivator that is recruited to MHC class II promoters by multiple synergistic interactions with an enhanceosome complex. In: Genes & development, 2000, vol. 14, n° 9, p. 1156–1166.
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ISSN of the journal0890-9369
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