Expression of MHC class II molecules in different cellular and functional compartments is controlled by differential usage of multiple promoters of the transactivator CIITA.
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.
Muhlethaler-Mottet
A
A
Department of Genetics and Microbiology, University of Geneva Medical School, Switzerland.
Otten
L A
LA
Steimle
V
V
Mach
B
B
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
D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators