title: Expression of MHC class II molecules in different cellular and functional compartments is controlled by differential usage of multiple promoters of the transactivator CIITA.
abstract: 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.
authors.affiliation: Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Muhlethaler-Mottet
authors.forename: L A
authors.initials: LA
authors.lastname: Otten
authors.forename: V
authors.initials: V
authors.lastname: Steimle
authors.forename: B
authors.initials: B
authors.lastname: Mach
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002451:Cell Compartmentation; D002460:Cell Line; D003001:Cloning, Molecular; D018507:Gene Expression Regulation, Developmental; D005802:Genes, MHC Class II; D017930:Genes, Reporter; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014018:Tissue Distribution; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators