PMID:10490661

Citation	Harris, MB, Chang, CC, Berton, MT, Danial, NN, Zhang, J, Kuehner, D, Ye, BH, Kvatyuk, M, Pandolfi, PP, Cattoretti, G, Dalla-Favera, R and Rothman, PB (1999) Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: specific regulation of iepsilon transcription and immunoglobulin E switching. Mol. Cell. Biol. 19:7264-75
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 epsilon 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 epsilon 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.
Links	PubMed PMC84719
Keywords	Animals; B-Lymphocytes/immunology; Binding Sites; DNA-Binding Proteins/metabolism; Gene Expression Regulation; Germ Cells/metabolism; Immunoglobulin Class Switching; Immunoglobulin E/genetics; Interleukin-4/pharmacology; Mice; Mice, Knockout; Protein Binding; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-bcl-6; STAT6 Transcription Factor; Signal Transduction; Trans-Activators/genetics; Trans-Activators/metabolism; Transcription Factors/metabolism; Transcription, Genetic
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