Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: Specific regulation of Iε transcription and immunoglobulin E switching Journal Article
| Authors: | 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. |
| Article Title: | Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: Specific regulation of Iε transcription and immunoglobulin E switching |
| 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. |
| Keywords: | signal transduction; dna-binding proteins; proto-oncogene proteins; nonhuman; binding affinity; mouse; animals; mice; mice, knockout; gene targeting; proto oncogene; gene expression; interleukin 4; protein binding; transcription, genetic; animalia; b-lymphocytes; transcription factors; gene expression regulation; germ cells; transcription regulation; binding site; binding sites; trans-activators; gene induction; immunoglobulin class switching; gene switching; helper cell; immunoglobulin e; interleukin-4; proto-oncogene proteins c-bcl-6; stat6 protein; priority journal; article; stat6 transcription factor |
| Journal Title: | Molecular and Cellular Biology |
| Volume: | 19 |
| Issue: | 10 |
| ISSN: | 0270-7306 |
| Publisher: | American Society for Microbiology |
| Date Published: | 1999-10-01 |
| Start Page: | 7264 |
| End Page: | 7275 |
| Language: | English |
| PUBMED: | 10490661 |
| PROVIDER: | scopus |
| PMCID: | PMC84719 |
| DOI: | 10.1128/MCB.19.10.7264 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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