Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination

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. (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)

URL: http://www.ncbi.nlm.nih.gov/pubmed/16678101
DOI: 10.1016/j.cell.2006.02.046

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 Deposited: 23 Jul 2015 20:10
Last Modified: 23 Jul 2015 20:10
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31659

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