Source:http://linkedlifedata.com/resource/pubmed/id/18280186
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
2008-3-17
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| pubmed:databankReference | |
| pubmed:abstractText |
Productive rearrangement of the immunoglobulin heavy-chain locus triggers a major developmental checkpoint that promotes limited clonal expansion of pre-B cells, thereby culminating in cell-cycle arrest and rearrangement of light-chain loci. By using Irf4-/-Irf8-/- pre-B cells, we demonstrated that two pathways converge to synergistically drive light-chain rearrangement, but not simply as a consequence of cell-cycle exit. One pathway was directly dependent on transcription factor IRF-4, whose expression was elevated by pre-B cell receptor signaling. IRF-4 targeted the immunoglobulin 3'Ekappa and Elambda enhancers and positioned a kappa allele away from pericentromeric heterochromatin. The other pathway was triggered by attenuation of IL-7 signaling and activated the iEkappa enhancer via binding of the transcription factor E2A. IRF-4 also regulated expression of chemokine receptor Cxcr4 and promoted migration of pre-B cells in response to the chemokine ligand CXCL12. We propose that IRF-4 coordinates the two pathways regulating light-chain recombination by positioning pre-B cells away from IL-7-expressing stromal cells.
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| pubmed:grant | |
| pubmed:commentsCorrections | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
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| pubmed:issn |
1097-4180
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
28
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
335-45
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| pubmed:dateRevised |
2009-5-21
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| pubmed:meshHeading |
pubmed-meshheading:18280186-Animals,
pubmed-meshheading:18280186-B-Lymphocytes,
pubmed-meshheading:18280186-Blotting, Western,
pubmed-meshheading:18280186-Cell Differentiation,
pubmed-meshheading:18280186-Cell Movement,
pubmed-meshheading:18280186-Electrophoretic Mobility Shift Assay,
pubmed-meshheading:18280186-Flow Cytometry,
pubmed-meshheading:18280186-Gene Rearrangement, B-Lymphocyte, Light Chain,
pubmed-meshheading:18280186-Immunoprecipitation,
pubmed-meshheading:18280186-In Situ Hybridization, Fluorescence,
pubmed-meshheading:18280186-Interferon Regulatory Factors,
pubmed-meshheading:18280186-Interleukin-7,
pubmed-meshheading:18280186-Mice,
pubmed-meshheading:18280186-Mice, Mutant Strains,
pubmed-meshheading:18280186-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:18280186-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:18280186-Signal Transduction,
pubmed-meshheading:18280186-Stem Cells
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| pubmed:year |
2008
|
| pubmed:articleTitle |
Regulation of immunoglobulin light-chain recombination by the transcription factor IRF-4 and the attenuation of interleukin-7 signaling.
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| pubmed:affiliation |
Department of Molecular Genetics and Cell Biology, University of Chicago, 929 East 57(th) Street, GCIS W522, Chicago, IL 60637, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|