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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2011-7-4
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pubmed:databankReference |
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pubmed:abstractText |
The co-occupancy of Tcf3 with Oct4, Sox2 and Nanog on embryonic stem cell (ESC) chromatin indicated that Tcf3 has been suggested to play an integral role in a poorly understood mechanism underlying Wnt-dependent stimulation of mouse ESC self-renewal of mouse ESCs. Although the conventional view of Tcf proteins as the ?-catenin-binding effectors of Wnt signalling suggested Tcf3-?-catenin activation of target genes would stimulate self-renewal, here we show that an antagonistic relationship between Wnt3a and Tcf3 on gene expression regulates ESC self-renewal. Genetic ablation of Tcf3 replaced the requirement for exogenous Wnt3a or GSK3 inhibition for ESC self-renewal, demonstrating that inhibition of Tcf3 repressor is the necessary downstream effect of Wnt signalling. Interestingly, both Tcf3-?-catenin and Tcf1-?-catenin interactions contributed to Wnt stimulation of self-renewal and gene expression, and the combination of Tcf3 and Tcf1 recruited Wnt-stabilized ?-catenin to Oct4 binding sites on ESC chromatin. This work elucidates the molecular link between the effects of Wnt and the regulation of the Oct4/Sox2/Nanog network.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM065400-01,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM065400-02,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM065400-03,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM065400-04,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM065400-05,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM065400-06,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM065400-07,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM065400-08,
http://linkedlifedata.com/resource/pubmed/grant/R01 GM065400-09,
http://linkedlifedata.com/resource/pubmed/grant/R01-CA128571,
http://linkedlifedata.com/resource/pubmed/grant/R01-GM065400
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pubmed:commentsCorrections |
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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/Basic Helix-Loop-Helix...,
http://linkedlifedata.com/resource/pubmed/chemical/Catnb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Nuclear Factor 1-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Hnf1a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Homeodomain Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nanog protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Octamer Transcription Factor-3,
http://linkedlifedata.com/resource/pubmed/chemical/Pou5f1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/SOXB1 Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Sox2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Tcf3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt3A Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt3a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1476-4679
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
762-70
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:21685894-Animals,
pubmed-meshheading:21685894-Basic Helix-Loop-Helix Transcription Factors,
pubmed-meshheading:21685894-Cell Line,
pubmed-meshheading:21685894-Cell Proliferation,
pubmed-meshheading:21685894-Embryonic Stem Cells,
pubmed-meshheading:21685894-Gene Expression Regulation, Developmental,
pubmed-meshheading:21685894-Glycogen Synthase Kinase 3,
pubmed-meshheading:21685894-Hepatocyte Nuclear Factor 1-alpha,
pubmed-meshheading:21685894-Homeodomain Proteins,
pubmed-meshheading:21685894-Mice,
pubmed-meshheading:21685894-Octamer Transcription Factor-3,
pubmed-meshheading:21685894-Protein Kinase Inhibitors,
pubmed-meshheading:21685894-RNA Interference,
pubmed-meshheading:21685894-SOXB1 Transcription Factors,
pubmed-meshheading:21685894-Signal Transduction,
pubmed-meshheading:21685894-Transcription, Genetic,
pubmed-meshheading:21685894-Transfection,
pubmed-meshheading:21685894-Wnt Proteins,
pubmed-meshheading:21685894-Wnt3 Protein,
pubmed-meshheading:21685894-Wnt3A Protein,
pubmed-meshheading:21685894-beta Catenin
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pubmed:year |
2011
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pubmed:articleTitle |
Opposing effects of Tcf3 and Tcf1 control Wnt stimulation of embryonic stem cell self-renewal.
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pubmed:affiliation |
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, 900 S Ashland Avenue, MBRB 2270, M/C 669, Chicago, Illinois 60607, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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