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

Masternak, Krzysztof; Muhlethaler-Mottet, Annick; Villard, Jean; Zufferey, Madeleine; Steimle, Viktor; Reith, Walter

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Title		CIITA is a transcriptional coactivator that is recruited to MHC class II promoters by multiple synergistic interactions with an enhanceosome complex
Authors		Masternak, Krzysztof Muhlethaler-Mottet, Annick Villard, Jean Zufferey, Madeleine Steimle, Viktor Reith, Walter
Published in		Genes and Development. 2000, vol. 14, no. 9, p. 1156-1166
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
Identifiers		PMID: 10809673
Full text		Article - Limited access to UNIGE Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC316580/pdf/x4.pdf
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 and Development, 2000, vol. 14, n° 9, p. 1156-1166. https://archive-ouverte.unige.ch/unige:11447