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

Research output: Contribution to journalArticle

154 Scopus citations

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
DOIs
StatePublished - Oct 1999
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    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. https://doi.org/10.1128/mcb.19.10.7264