Activation and transdominant suppression of MHC class II and HLA-DMB promoters by a series of C-terminal class II transactivator deletion mutants.
The class II transactivator (CIITA) is a highly specific transcription factor that activates only genes known to be involved in the class II MHC processing pathway, including class II MHC, invariant chain, and HLA-DMA/B genes. In this work, we show the requirement of a new region in CIITA that is critical for its function. Deletion mutants lacking varying length of the C terminus show that the C-terminal 41 amino acids of CIITA are indispensable for the activation of both the conventional DRA and nonconventional DMB promoters. This region contains a highly charged stretch of amino acids that is homologous to a yeast transcription factor, repression activator protein-1 (RAP1)-interacting factor 1. Mutants lacking the C terminus were tested in a transdominant-negative assay to examine their capacity to block the wild-type CIITA function. Two of these deletion mutants suppressed the activity of endogenously expressed wild-type CIITA to activate both DRA and DMB promoters. It may be possible to utilize these mutants to modulate MHC class II and DM gene expression.
Chin
K C
KC
Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 27599-7295, USA.
Li
G
G
Ting
J P
JP
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D017353:Gene Deletion; D006681:HLA-D Antigens / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*
C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II