Induction of BCL-6 gene expression by interferon-gamma and identification of an IRE in exon I.
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-gamma in Jurkat cells and in nontransformed T cells polarized toward the Th1 phenotype. The IFN-gamma-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-gamma. A guanine at +195 residing at the boundary of the X-box and a downstream IFN-gamma-activated sequence ( GAS 1; between nucleotides +192 to +200) is occupied in IFN-gamma-treated cells, indicating the interaction of an IFN-gamma-inducible/modified factor to this region. Consistent with this, electrophoretic mobility shift assays detect STAT-1alpha interactions with the downstream GAS1 motif. The cumulative data suggest that the X-box-binding protein facilitate the binding of STAT-1alpha to the GAS 1 site. The discovery that the BCL-6 transcription factor is inducible by IFN-gamma 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.[1]References
- Induction of BCL-6 gene expression by interferon-gamma and identification of an IRE in exon I. Zhou, G., Ono, S.J. Exp. Mol. Pathol. (2005) [Pubmed]
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