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 expresse d in B cells, activated T lymphocytes, and in antigen-presenting cells . In addition, HLA-DRA gene expression is inducible in a variety of ce ll types by interferon-gamma (IFN-gamma). Here we show that the lympho id-specific transcription factor Oct-2A plays a critical role in HLA-D RA gene expression in class II-positive B cell lines, and that the hig h 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 a nd 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 HL A-DRA gene in HeLa cells, but antisense HMG I/Y dramatically decreases the level of induction. We conclude that distinct sets of transcripti on factors are involved in the two modes of HLA-DRA expression, and th at HMG I/Y may be important for B cell-specific expression, and is ess ential for IFN-gamma induction.