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A functionally essential domain of RFX5 mediates activation of major histocompatibility complex class II promoters by promoting cooperative binding between RFX and NF-Y
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Villard J Peretti M Masternak K Barras E Caretti G Mantovani R Reith W 《Molecular and cellular biology》2000,20(10):3364-3376
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Expression of MHC class II molecules in different cellular and functional compartments is controlled by differential usage of multiple promoters of the transactivator CIITA. 总被引:5,自引:0,他引:5
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The highly complex pattern of expression of major histocompatibility complex class II (MHC-II) molecules determines both the immune repertoire during development and subsequently the triggering and the control of immune responses. These distinct functions result from cell type-restricted expression, developmental control and either constitutive or inducible expression of MHC-II genes. Yet, in these various situations, MHC-II gene expression is always under the control of a unique transactivator, CIITA. Here we show that the CIITA gene is controlled by several distinct promoters, two of which direct specific constitutive expression in dendritic cells and B lymphocytes respectively, while another mediates gamma-interferon-induced expression. Thus the cellular, temporal and functional diversity of MHC-II expression is ultimately controlled by differential activation of different promoters of a single transactivator gene. This provides novel experimental tools to dissect compartment-specific gain or loss of MHC-II function in vivo. 相似文献
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Analysis of ankyrin repeats reveals how a single point mutation in RFXANK results in bare lymphocyte syndrome.
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N Nekrep M Geyer N Jabrane-Ferrat B M Peterlin 《Molecular and cellular biology》2001,21(16):5566-5576
Ankyrin repeats are well-known structural modules that mediate interactions between a wide spectrum of proteins. The regulatory factor X with ankyrin repeats (RFXANK) is a subunit of a tripartite RFX complex that assembles on promoters of major histocompatibility complex class II (MHC II) genes. Although it is known that RFXANK plays a central role in the nucleation of RFX, it was not clear how its ankyrin repeats mediate the interactions within the complex and with other proteins. To answer this question, we modeled the RFXANK protein and determined the variable residues of the ankyrin repeats that should contact other proteins. Site-directed alanine mutagenesis of these residues together with in vitro and in vivo binding studies elucidated how RFXAP and CIITA, which simultaneously interact with RFXANK in vivo, bind to two opposite faces of its ankyrin repeats. Moreover, the binding of RFXAP requires two separate surfaces on RFXANK. One of them, which is located in the ankyrin groove, is severely affected in the FZA patient with the bare lymphocyte syndrome. This genetic disease blocks the expression of MHC II molecules on the surface of B cells. By pinpointing the interacting residues of the ankyrin repeats of RFXANK, the mechanism of this subtype of severe combined immunodeficiency was revealed. 相似文献
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MHC II类分子表达调控的研究进展 总被引:1,自引:0,他引:1
MHCII类分子提呈经过加工的抗原给CD4 T淋巴细胞 ,在诱发免疫反应中起重要作用。MHCII类分子不正常表达会引起严重的免疫缺陷疾病 ,如裸淋巴细胞综合征 (BLS)等。目前已识别出四种不同的MHCII调控基因。这些基因分别编码RFXANK、RFX5、RFXAP和CIITA。其中 ,前三个是RFX复合物的亚基 ,RFX是一种结合于所有MHCII类基因启动子上的泛式表达的因子。CIITA是MHCII类分子表达的主要调控因子 ,其严密调控的表达模式决定了MHCII类分子表达的细胞特异性 ,及能否被诱导且在何种水平上表达。本文着重介绍近年来国内外对MHCII类分子表达及其调控研究的新进展 相似文献
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