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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2011-5-12
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pubmed:abstractText |
The HMG-box transcription factor LEF1 controls many developmentally regulated genes, including genes that activate expression of the T-cell antigen receptor alpha chain (TCR-alpha) in developing thymocytes. At least two distinct isoforms of LEF1 are expressed, resulting from variable inclusion of LEF1 exon 6; however, the expression pattern of these isoforms and mechanism of splicing regulation have not been explored. Here we demonstrate that inclusion of LEF1 exon 6 is increased during thymic development and in response to signaling in a cultured T-cell line in a manner which temporally correlates with increased expression of TCR-alpha. We further find that inclusion of exon 6 is dependent on the signal-induced increase in expression and binding of the splicing factor CELF2 to two intronic sequences flanking the regulated exon. Importantly, loss of exon 6 inclusion, through knockdown of CELF2 or direct block of the exon 6 splice site, results in reduced expression of TCR-alpha mRNA. Together, these data establish the mechanistic basis of LEF1 splicing regulation and demonstrate that LEF1 alternative splicing is a contributing determinant in the optimal expression of the TCR-alpha chain.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/CELF2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/LEF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphoid Enhancer-Binding Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/RNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell...,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1098-5549
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
31
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2184-95
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
pubmed-meshheading:21444716-Alternative Splicing,
pubmed-meshheading:21444716-Animals,
pubmed-meshheading:21444716-Base Sequence,
pubmed-meshheading:21444716-Blotting, Western,
pubmed-meshheading:21444716-Cell Line,
pubmed-meshheading:21444716-Exons,
pubmed-meshheading:21444716-Gene Knockdown Techniques,
pubmed-meshheading:21444716-Humans,
pubmed-meshheading:21444716-Lymphocyte Activation,
pubmed-meshheading:21444716-Lymphoid Enhancer-Binding Factor 1,
pubmed-meshheading:21444716-Mice,
pubmed-meshheading:21444716-Molecular Sequence Data,
pubmed-meshheading:21444716-Nerve Tissue Proteins,
pubmed-meshheading:21444716-Polymerase Chain Reaction,
pubmed-meshheading:21444716-Protein Isoforms,
pubmed-meshheading:21444716-RNA-Binding Proteins,
pubmed-meshheading:21444716-Receptors, Antigen, T-Cell, alpha-beta,
pubmed-meshheading:21444716-T-Lymphocytes,
pubmed-meshheading:21444716-Tetradecanoylphorbol Acetate,
pubmed-meshheading:21444716-Thymus Gland
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pubmed:year |
2011
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pubmed:articleTitle |
Signal- and development-dependent alternative splicing of LEF1 in T cells is controlled by CELF2.
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pubmed:affiliation |
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, 422 Curie Blvd, Philadelphia, PA 19104-6059, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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