Functional roles of the transcription factor oct-2a and the high mobility group protein i/y in hla-dra gene expression

Sarki Abba Abdulkadir, Srikant Krishna, Dimitris Thanos, Tom Maniatis, Jack L. Strominger, Santa Jeremy Ono

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

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-γ), (IFN-γ). 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 DP, A 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-γ induction of the HLA-DILA 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-γ induction.

Original languageEnglish (US)
Pages (from-to)487-500
Number of pages14
JournalJournal of Experimental Medicine
Volume182
Issue number2
DOIs
StatePublished - Aug 1 1995

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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