Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: Specific regulation of Iε transcription and immunoglobulin E switching

Miera B. Harris, Chih Chao Chang, Michael T. Berton, Nika N. Danial, Jandong Zhang, Denise Kuehner, Bihui H. Ye, Marina Kvatyuk, Pier Paolo Pandolfi, Giorgio Cattoretti, Riccardo Dalla-Favera, Paul B. Rothman

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Abstract

The BCL-6 proto-oncogene encodes a POZ/zinc-finger transcription factor that is expressed in B cells and a subset of CD4+ T cells within germinal centers. Recent evidence suggests that BCL-6 can act as a sequence-specific repressor of transcription, but the target genes for this activity have not yet been identified. The binding site for BCL-6 shares striking homology to the sites that are the target sequence for the interleukin-4 (IL-4)-induced Stat6 (signal transducers and activators of transcription) signaling molecule. Electrophoretic mobility shift assays demonstrate that BCL-6 can bind, with different affinities, to several DNA elements recognized by Stat6. Expression of BCL-6 can repress the IL-4-dependent induction of immunoglobulin (Ig) germ line ε transcripts, but does not repress the IL-4 induction of CD23 transcripts. Consistent with the role of BCL-6 in modulating transcription from the germ line ε promoter, BCL-6(-/-) mice display an increased ability to class switch to IgE in response to IL-4 in vitro. These animals also exhibit a multiorgan inflammatory disease characterized by the presence of a large number of IgE+ B cells. The apparent dysregulation of IgE production is abolished in BCL-6(-/-) Stat6(-/- ) mice, indicating that BCL-6 regulation of Ig class switching is dependent upon Stat6 signaling. Thus, BCL-6 can modulate the transcription of selective Stat6-dependent IL-4 responses, including IgE class switching in B cells.

Original languageEnglish (US)
Pages (from-to)7264-7275
Number of pages12
JournalMolecular and cellular biology
Volume19
Issue number10
StatePublished - Oct 1 1999

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Harris, M. B., Chang, C. C., Berton, M. T., Danial, N. N., Zhang, J., Kuehner, D., Ye, B. H., Kvatyuk, M., Pandolfi, P. P., Cattoretti, G., Dalla-Favera, R., & Rothman, P. B. (1999). Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: Specific regulation of Iε transcription and immunoglobulin E switching. Molecular and cellular biology, 19(10), 7264-7275.