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, B. Hilda 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 1999
Externally publishedYes

Fingerprint

Interleukin-4
Immunoglobulin E
Immunoglobulin Class Switching
Genes
Germ Cells
B-Lymphocytes
B-Lymphocyte Subsets
Germinal Center
Proto-Oncogenes
Zinc Fingers
Electrophoretic Mobility Shift Assay
Transducers
Immunoglobulins
Transcription Factors
Binding Sites
T-Lymphocytes
DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Harris, M. B., Chang, C. C., Berton, M. T., Danial, N. N., Zhang, J., Kuehner, D., ... 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.

Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6 : Specific regulation of Iε transcription and immunoglobulin E switching. / Harris, Miera B.; Chang, Chih Chao; Berton, Michael T.; Danial, Nika N.; Zhang, Jandong; Kuehner, Denise; Ye, B. Hilda; Kvatyuk, Marina; Pandolfi, Pier Paolo; Cattoretti, Giorgio; Dalla-Favera, Riccardo; Rothman, Paul B.

In: Molecular and Cellular Biology, Vol. 19, No. 10, 10.1999, p. 7264-7275.

Research output: Contribution to journalArticle

Harris, MB, Chang, CC, Berton, MT, Danial, NN, Zhang, J, Kuehner, D, Ye, BH, Kvatyuk, M, Pandolfi, PP, Cattoretti, G, Dalla-Favera, R & Rothman, PB 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, vol. 19, no. 10, pp. 7264-7275.
Harris, Miera B. ; Chang, Chih Chao ; Berton, Michael T. ; Danial, Nika N. ; Zhang, Jandong ; Kuehner, Denise ; Ye, B. Hilda ; Kvatyuk, Marina ; Pandolfi, Pier Paolo ; Cattoretti, Giorgio ; Dalla-Favera, Riccardo ; Rothman, Paul B. / Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6 : Specific regulation of Iε transcription and immunoglobulin E switching. In: Molecular and Cellular Biology. 1999 ; Vol. 19, No. 10. pp. 7264-7275.
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AU - Kvatyuk, Marina

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AU - Dalla-Favera, Riccardo

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