Class II transactivator is required for maximal expression of HLA-DOB in B cells.
HLA-DO, encoded by the HLA-DOA and HLA-DOB genes, has been shown to function as a modulator of Ag presentation. DNA microarray comparisons between B cells wild-type and mutant for the master regulator of MHC class II transcription, class II transactivator (CIITA), identified HLA-DOA and HLA-DOB as being up-regulated by CIITA. Although HLA-DOA had been shown previously to be regulated by CIITA, HLA-DOB expression was suggested to be independent of CIITA. A series of assays including quantitative RT-PCR, promoter-reporter assays, chromatin immunoprecipitations, and intracellular staining were performed to corroborate the DNA microarray analysis. The combined data demonstrate that HLA-DOB levels are increased by CIITA, and that this difference has an impact on the overall level of HLA-DO expression. Additionally, unlike the classical MHC class II genes, HLA-DOB expression was present in the absence of CIITA, indicating that additional factors mediate HLA-DOB expression in B cells.
Nagarajan
Uma M
UM
Department of Microbiology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Lochamy
Jonathan
J
Chen
Xinjian
X
Beresford
Guy W
GW
Nilsen
Roger
R
Jensen
Peter E
PE
Boss
Jeremy M
JM
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D020869:Gene Expression Profiling; D017930:Genes, Reporter; D006681:HLA-D Antigens / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000096:biosynthesis; D000071701:Regulatory Factor X Transcription Factors; D020218:Response Elements; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D004268:DNA-Binding Proteins; D006681:HLA-D Antigens; C046148:HLA-DO antigens; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; C093524:RFX5 protein, human; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators