The fully linked HTML version of this article has now been published.
JCS ePress
online publication date 22 Feb 2005
doi: 10.1242/jcs.01706
Research Article
PITX2, 
-catenin and LEF-1 interact to synergistically regulate the LEF-1 promoter
Usha Vadlamudi,
Herbert M. Espinoza,
Mrudula Ganga,
Donna M. Martin,
Xiaoming Liu,
John F. Engelhardt,
and
Brad A. Amendt*
* Author for correspondence (e-mail: bamendt{at}ibt.tamhsc.edu)
PITX2, 
-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, -catenin in combination with PITX2 synergistically activates the LEF-1 promoter and this activation is independent of the Wnt-responsive element. -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 -catenin direct physical interactions. LEF-1 and -catenin interactions with PITX2 provide new mechanisms for the regulation of PITX2 transcriptional activity.
This article has been cited by other articles:
|
|
|
|
 
S. R. Venugopalan, M. A. Amen, J. Wang, L. Wong, A. C. Cavender, R. N. D'Souza, M. Akerlund, S. L. Brody, T. A. Hjalt, and B. A. Amendt
Novel expression and transcriptional regulation of FoxJ1 during oro-facial morphogenesis
Hum. Mol. Genet.,
December 1, 2008;
17(23):
3643 - 3654.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tessari, M. Pietrobon, A. Notte, G. Cifelli, P. J. Gage, M. D. Schneider, G. Lembo, and M. Campione
Myocardial Pitx2 Differentially Regulates the Left Atrial Identity and Ventricular Asymmetric Remodeling Programs
Circ. Res.,
April 11, 2008;
102(7):
813 - 822.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Fretz, N. K. Shevde, S. Singh, B. G. Darnay, and J. W. Pike
Receptor Activator of Nuclear Factor-{kappa}B Ligand-Induced Nuclear Factor of Activated T Cells (C1) Autoregulates Its Own Expression in Osteoclasts and Mediates the Up-Regulation of Tartrate-Resistant Acid Phosphatase
Mol. Endocrinol.,
March 1, 2008;
22(3):
737 - 750.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Amen, H. M. Espinoza, C. Cox, X. Liang, J. Wang, T. M. E. Link, R. G. Brennan, J. F. Martin, and B. A. Amendt
Chromatin-associated HMG-17 is a major regulator of homeodomain transcription factor activity modulated by Wnt/{beta}-catenin signaling
Nucleic Acids Res.,
February 2, 2008;
36(2):
462 - 476.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. A. Atcha, A. Syed, B. Wu, N. P. Hoverter, N. N. Yokoyama, J.-H. T. Ting, J. E. Munguia, H. J. Mangalam, J. L. Marsh, and M. L. Waterman
A Unique DNA Binding Domain Converts T-Cell Factors into Strong Wnt Effectors
Mol. Cell. Biol.,
December 1, 2007;
27(23):
8352 - 8363.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Amen, X. Liu, U. Vadlamudi, G. Elizondo, E. Diamond, J. F. Engelhardt, and B. A. Amendt
PITX2 and {beta}-Catenin Interactions Regulate Lef-1 Isoform Expression
Mol. Cell. Biol.,
November 1, 2007;
27(21):
7560 - 7573.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Ai, J. Wang, M. Amen, M.-F. Lu, B. A. Amendt, and J. F. Martin
Nuclear Factor 1 and T-Cell Factor/LEF Recognition Elements Regulate Pitx2 Transcription in Pituitary Development
Mol. Cell. Biol.,
August 15, 2007;
27(16):
5765 - 5775.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Diamond, M. Amen, Q. Hu, H. M. Espinoza, and B. A. Amendt
Functional interactions between Dlx2 and lymphoid enhancer factor regulate Msx2
Nucleic Acids Res.,
November 6, 2006;
34(20):
5951 - 5965.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. W.-H. Li, J.-H. T. Ting, N. N. Yokoyama, A. Bernstein, M. van de Wetering, and M. L. Waterman
Wnt Activation and Alternative Promoter Repression of LEF1 in Colon Cancer.
Mol. Cell. Biol.,
July 1, 2006;
26(14):
5284 - 5299.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Bidinost, M. Matsumoto, D. Chung, N. Salem, K. Zhang, D. W. Stockton, A. Khoury, A. Megarbane, B. A. Bejjani, and E. I. Traboulsi
Heterozygous and Homozygous Mutations in PITX3 in a Large Lebanese Family with Posterior Polar Cataracts and Neurodevelopmental Abnormalities.
Invest. Ophthalmol. Vis. Sci.,
April 1, 2006;
47(4):
1274 - 1280.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Evans and P. J. Gage
Expression of the homeobox gene Pitx2 in neural crest is required for optic stalk and ocular anterior segment development
Hum. Mol. Genet.,
November 15, 2005;
14(22):
3347 - 3359.
[Abstract]
[Full Text]
[PDF]
|
|
|
© The Company of Biologists Ltd 2005
