Induction of BCL-6 gene expression by interferon-γ and identification of an IRE in exon I

Gang Zhou, Santa Jeremy Ono

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

BCL-6 is a POZ domain zinc-finger transcription factor that appears to play important roles in the development of the immune system and its regulation. Mutations within BCL-6 gene can therefore contribute to the genesis of a variety of lymphomas, and can also manifest as a classic Th2-type hyperimmune response. In addition to its roles in B- and T-cell development, and in germinal centre formation, the factor is also critical for the development of peripheral memory T cells. In this study, we report that BCL-6 expression is induced by IFN-γ in Jurkat cells and in nontransformed T cells polarized toward the Th1 phenotype. The IFN-γ-responsive region has been mapped within the first exon between nucleotide +180 and +200. In vivo footprinting of the first exon reveals that a stretch of DNA between nucleotide +180 to +195 (which we term the X-box) is constitutively occupied in vivo in the presence or absence of IFN-γ. A guanine at +195 residing at the boundary of the X-box and a downstream IFN-γ-activated sequence (GAS 1; between nucleotides +192 to +200) is occupied in IFN-γ-treated cells, indicating the interaction of an IFN-γ-inducible/modified factor to this region. Consistent with this, electrophoretic mobility shift assays detect STAT-1α interactions with the downstream GAS1 motif. The cumulative data suggest that the X-box-binding protein facilitate the binding of STAT-1α to the GAS 1 site. The discovery that the BCL-6 transcription factor is inducible by IFN-γ may help explain some of the postulated biological roles of BCL-6 in T cell development and differentiation, and help explain the Th2-biased phenotype of BCL-6-deficient mice.

Original languageEnglish (US)
Pages (from-to)25-35
Number of pages11
JournalExperimental and Molecular Pathology
Volume78
Issue number1
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

Keywords

  • BCL-6 gene
  • Interferon-γ
  • Mice

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry

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