Functional roles of the transcription factor Oct-2A and the high mobility group protein I/Y in HLA-DRA gene expression.
The class II major histocompatibility complex gene HLA-DRA is expressed in B cells, activated T lymphocytes, and in antigen-presenting cells. In addition, HLA-DRA gene expression is inducible in a variety of cell types by interferon-gamma (IFN-gamma). Here we show that the lymphoid-specific transcription factor Oct-2A plays a critical role in HLA-DRA gene expression in class II-positive B cell lines, and that the high mobility group protein (HMG) I/Y binds to multiple sites within the DRA promoter, including the Oct-2A binding site. Coexpression of HMG I/Y and Oct-2 in cell lines lacking Oct-2 results in high levels of HLA-DRA gene expression, and in vitro DNA-binding studies reveal that HMG I/Y stimulates Oct-2A binding to the HLA-DRA promoter. Thus, Oct-2A and HMG I/Y may synergize to activate HLA-DRA expression in B cells. By contrast, Oct-2A is not involved in the IFN-gamma induction of the HLA-DRA gene in HeLa cells, but antisense HMG I/Y dramatically decreases the level of induction. We conclude that distinct sets of transcription factors are involved in the two modes of HLA-DRA expression, and that HMG I/Y may be important for B cell-specific expression, and is essential for IFN-gamma induction.
Abdulkadir
S A
SA
Department of Medicine, Lucille P. Markey Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore 21224, USA.
Krishna
S
S
Thanos
D
D
Maniatis
T
T
Strominger
J L
JL
Ono
S J
SJ
D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059805:HLA-DR alpha-Chains; D025741:HMGA1a Protein; D006367:HeLa Cells; D006609:High Mobility Group Proteins / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D008214:Lymphocytes / Q000502:physiology; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D050813:Octamer Transcription Factor-2; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D017931:DNA Primers; D004268:DNA-Binding Proteins; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C057615:HLA-DQbeta antigen; D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; D006609:High Mobility Group Proteins; D046911:Macromolecular Substances; D050813:Octamer Transcription Factor-2; C058435:POU2F2 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D025741:HMGA1a Protein; D007371:Interferon-gamma