Olson, L. E., Tollkuhn, J., Scafoglio, C., Krones, A., Zhang, J., Ohgi, K. A., Wu, W., Taketo, M. M., Kemler, R., Grosschedl, R., Rose, D., Li, X., Rosenfeld, M. G. (May 2006) Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination. Cell, 125 (3). pp. 593-605. ISSN 0092-8674 (Print)0092-8674 (Linking)
Abstract
While the biological roles of canonical Wnt/beta-catenin signaling in development and disease are well documented, understanding the molecular logic underlying the functionally distinct nuclear transcriptional programs mediating the diverse functions of beta-catenin remains a major challenge. Here, we report an unexpected strategy for beta-catenin-dependent regulation of cell-lineage determination based on interactions between beta-catenin and a specific homeodomain factor, Prop1, rather than Lef/Tcfs. beta-catenin acts as a binary switch to simultaneously activate expression of the critical lineage-determining transcription factor, Pit1, and to repress the gene encoding the lineage-inhibiting transcription factor, Hesx1, acting via TLE/Reptin/HDAC1 corepressor complexes. The strategy of functionally distinct actions of a homeodomain factor in response to Wnt signaling is suggested to be prototypic of a widely used mechanism for generating diverse cell types from pluripotent precursor cells in response to common signaling pathways during organogenesis.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Animals Cell Differentiation/physiology Cell Lineage/ physiology HeLa Cells Histone Deacetylase 1 Histone Deacetylases/metabolism Homeodomain Proteins/ metabolism Humans Lymphoid Enhancer-Binding Factor 1/metabolism Mice Mice, Knockout Mice, Transgenic Organogenesis/physiology Repressor Proteins/metabolism Signal Transduction/ physiology Transcription Factor Pit-1/metabolism Transcriptional Activation/physiology Wnt Proteins/ metabolism beta Catenin/ metabolism |
| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > homeodomain protein organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > progenitor cell |
| CSHL Authors: | |
| Communities: | CSHL labs > Tollkuhn lab |
| Depositing User: | Matt Covey |
| Date: | 5 May 2006 |
| Date Deposited: | 23 Jul 2015 20:10 |
| Last Modified: | 23 Jul 2015 20:10 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/31659 |
Actions (login required)
 |
Administrator's edit/view item |