Journal article
Antagonistic Regulation of Dlx2 Expression by PITX2 and Msx2: Implications for Tooth Development
Gene expression, Vol.9(6), pp.265-281
2001
DOI: 10.3727/000000001783992515
PMCID: PMC5964948
PMID: 11763998
Abstract
The transcriptional mechanisms underlying tooth development are only beginning to be understood. Pitx2, a bicoid-like homeodomain transcription factor, is the first transcriptional marker observed during tooth development. Because
Pitx2
,
Msx2
, and
Dlx2
are expressed in the dental epithelium, we examined the transcriptional activity of PITX2 in concert with Msx2 and the
Dlx2
promoter. PITX2 activated while Msx2 unexpectedly repressed transcription of a TK-
Bicoid
luciferase reporter in a tooth epithelial cell line (LS-8) and CHO cell line. Surprisingly, Msx2 binds to the
bicoid
element (5′-TAATCC-3′) with a high specificity and competes with PITX2 for binding to this element. PITX2 binds to
bicoid
and
bicoid
-like elements in the
Dlx2
promoter and activates this promoter 45-fold in CHO cells. However, it is only modestly activated in the LS-8 tooth epithelial cell line that endogenously expresses Msx2 and Pitx2. RT-PCR and Western blot assays reveal that two Pitx2 isoforms are expressed in the LS-8 cells. We further demonstrate that PITX2 dimerization can occur through the C-terminus of PITX2. Msx2 represses the
Dlx2
promoter in CHO cells and coexpression of both PITX2 and Msx2 resulted in transcriptional antagonism of the
Dlx2
promoter. Electrophoretic mobility shift assays demonstrate that factors in the LS-8 cell line specifically interact with PITX2. Thus,
Dlx2
gene transcription is regulated by antagonistic effects between PITX2, Msx2, and factors expressed in the tooth epithelia.
Details
- Title: Subtitle
- Antagonistic Regulation of Dlx2 Expression by PITX2 and Msx2: Implications for Tooth Development
- Creators
- Patrick D Green - Department of Biological Science, The University of TulsaTord A Hjalt - Department of Pediatrics, The University of IowaDianne E Kirk - Department of Biological Science, The University of TulsaLillian B Sutherland - Department of Physiology and Biophysics, The University of IowaBethan L Thomas - Department of Craniofacial Development, GKT Dental Institute, King’s College, University of LondonPaul T Sharpe - Department of Craniofacial Development, GKT Dental Institute, King’s College, University of LondonMalcolm L Snead - The Center for Craniofacial Molecular Biology, The University of Southern California, School of DentistryJeffrey C Murray - Department of Pediatrics, The University of IowaAndrew F Russo - Department of Physiology and Biophysics, The University of IowaBrad A Amendt - Department of Biological Science, The University of Tulsa
- Resource Type
- Journal article
- Publication Details
- Gene expression, Vol.9(6), pp.265-281
- DOI
- 10.3727/000000001783992515
- PMID
- 11763998
- PMCID
- PMC5964948
- NLM abbreviation
- Gene Expr
- ISSN
- 1052-2166
- eISSN
- 1555-3884
- Publisher
- Cognizant Communication Corporation; Elmsford, NY
- Alternative title
- REGULATION OF Dlx2 EXPRESSION
- Language
- English
- Date published
- 2001
- Academic Unit
- Neurology; Orthodontics; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Iowa Neuroscience Institute; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984020884902771
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