The DMB promoter: delineation, in vivo footprint, trans-activation, and trans-dominant suppression.
The HLA-DM loci encode the heterodimeric unconventional class II MHC molecules that are coexpressed with conventional class II MHC molecules. DM molecules are essential for the proper formation and function of conventional class II MHC molecules. This report characterizes the DMB promoter both by in vivo footprint and by in vitro functional analysis and reveals a promoter structure similar to that of conventional class II MHC genes. DR-negative mutant cell lines selectively defective in the transcription factor or class II trans-activator (CIITA) were used to reveal a requirement for both these factors in DMB promoter activation. Complementation of defective cell lines with the appropriate transcription factor reconstituted DMB promoter activation. Further analysis with CIITA identified several mutant forms of CIITA that are trans-dominant-negative mutants, i.e., they suppressed DMB promoter activation by transfected and endogenous CIITA. These mutants may be used in abiological setting to down-regulate the function of DM in Ag processing.
Ting
J P
JP
Lineberger Comprehensive Cancer Center and Department of Microbiology-Immunology, University of North Carolina, Chapel Hill 27514, USA.
Wright
K L
KL
Chin
K C
KC
Brickey
W J
WJ
Li
G
G
D001483:Base Sequence; D002460:Cell Line; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000502:physiology; D005802:Genes, MHC Class II; D006681:HLA-D Antigens / Q000235:genetics*; D000949:Histocompatibility Antigens Class II; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D014162:Transfection
D004268:DNA-Binding Proteins; C416189:H2-M antigens; D006681:HLA-D Antigens; C084245:HLA-DM antigens; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors