Journal article
PITX2, β-catenin and LEF-1 interact to synergistically regulate the LEF-1 promoter
Journal of cell science, Vol.118(6), pp.1129-1137
03/15/2005
DOI: 10.1242/jcs.01706
PMID: 15728254
Abstract
PITX2, β-catenin and lymphoid enhancer factor (LEF-1) are required for the inductive formation of several epithelial-derived organs, including teeth. Lef-1 is expressed in the dental epithelium after Pitx2, and both factors have overlapping expression patterns in the tooth bud and cap stages. Our analysis of Pitx2–/– mutant mice showed reduced Lef-1 expression in facial tissues by RT-PCR and quantitative RT-PCR. Consistent with these results we show that the human 2.5 kb LEF-1 promoter is activated by PITX2. Furthermore, the LEF-1 promoter is differentially activated by PITX2 isoforms, which are co-expressed in dental epithelium. The 2.5 kb LEF-1 promoter contains two regions that act to inhibit its transcription in concert with PITX2. The proximal region contains a Wnt-responsive element (WRE) that attenuates PITX2 activation. LEF-1 cannot autoregulate LEF-1 expression; however co-transfection of PITX2 and LEF-1 result in a synergistic activation of the 2.5 kb LEF-1 promoter. LEF-1 specifically interacts with the PITX2 C-terminal tail. Deletion of a distal 800 bp segment of the LEF-1 promoter resulted in enhanced PITX2 activation, and increased synergistic activation in the presence of LEF-1. Furthermore, β-catenin in combination with PITX2 synergistically activates the LEF-1 promoter and this activation is independent of the Wnt-responsive element. β-catenin directly interacts with PITX2 to synergistically regulate LEF-1 expression. We show a new mechanism where LEF-1 expression is regulated through PITX2, LEF-1 and β-catenin direct physical interactions. LEF-1 and β-catenin interactions with PITX2 provide new mechanisms for the regulation of PITX2 transcriptional activity.
Details
- Title: Subtitle
- PITX2, β-catenin and LEF-1 interact to synergistically regulate the LEF-1 promoter
- Creators
- Usha Vadlamudi - University of TulsaHerbert M. Espinoza - University of TulsaMrudula Ganga - University of TulsaDonna M. Martin - University of MichiganXiaoming Liu - University of IowaJohn F. Engelhardt - University of IowaBrad A. Amendt - University of Tulsa
- Resource Type
- Journal article
- Publication Details
- Journal of cell science, Vol.118(6), pp.1129-1137
- DOI
- 10.1242/jcs.01706
- PMID
- 15728254
- NLM abbreviation
- J Cell Sci
- ISSN
- 0021-9533
- eISSN
- 1477-9137
- Language
- English
- Date published
- 03/15/2005
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Orthodontics; Anatomy and Cell Biology; Radiation Oncology; Craniofacial Anomalies Research Center; Dental Research; Internal Medicine
- Record Identifier
- 9984284329802771
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