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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
2005-3-28
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pubmed:abstractText |
BCL-6 functions as a potent transcriptional repressor that binds with specificity to DNA elements bearing marked similarity to STAT recognition sequences. Previous studies have demonstrated that BCL-6 and Stat6 can both bind and regulate the Iepsilon promoter that controls immunoglobulin heavy chain class switching to IgE. Examination of BCL-6-/- and BCL-6-/-Stat6-/- mice has demonstrated that BCL-6 is a repressor of IgE and that Stat6 is still required for the interleukin-4 (IL-4) induction of class switching to IgE in B cells lacking BCL-6. To define the mechanisms by which BCL-6 represses IL-4 function, we analyzed the role of BCL-6 in repressing the Iepsilon promoter. There are three BCL-6-binding sites within this IL-4-responsive promoter. Analysis of Iepsilon promoters that have mutated BCL-6-binding sites demonstrates that at least two of these sites are required for maximal BCL-6 repression of this locus. Footprinting analysis demonstrates that BCL-6 binds cooperatively to the two upstream binding sites in the Iepsilon promoter. This cooperative binding requires the POZ domain of BCL-6. Furthermore, activated Stat6 molecules can displace BCL-6 from one of these binding sites. These data demonstrate that cooperative interaction between BCL-6 molecules is required for repression of the Iepsilon promoter.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
280
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13114-21
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:15659391-Animals,
pubmed-meshheading:15659391-Binding, Competitive,
pubmed-meshheading:15659391-Binding Sites,
pubmed-meshheading:15659391-CCAAT-Enhancer-Binding Protein-beta,
pubmed-meshheading:15659391-Cell Line,
pubmed-meshheading:15659391-DNA-Binding Proteins,
pubmed-meshheading:15659391-Deoxyribonuclease I,
pubmed-meshheading:15659391-Genes, Reporter,
pubmed-meshheading:15659391-Glutathione Transferase,
pubmed-meshheading:15659391-Interleukin-4,
pubmed-meshheading:15659391-Mice,
pubmed-meshheading:15659391-Mutation,
pubmed-meshheading:15659391-Plasmids,
pubmed-meshheading:15659391-Promoter Regions, Genetic,
pubmed-meshheading:15659391-Protein Binding,
pubmed-meshheading:15659391-Protein Structure, Tertiary,
pubmed-meshheading:15659391-Proto-Oncogene Proteins,
pubmed-meshheading:15659391-Proto-Oncogene Proteins c-bcl-6,
pubmed-meshheading:15659391-Recombinant Proteins,
pubmed-meshheading:15659391-Transcription, Genetic,
pubmed-meshheading:15659391-Transcription Factors,
pubmed-meshheading:15659391-Transfection
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pubmed:year |
2005
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pubmed:articleTitle |
Repression of an interleukin-4-responsive promoter requires cooperative BCL-6 function.
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pubmed:affiliation |
Integrated Program in Cellular, Molecular, and Biophysical Sciences and the Departments of Medicine and Microbiology, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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