Tbx1 Regulates the BMP-Smad1 Pathway in a Transcription Independent Manner
Open Access
- 25 June 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (6), e6049
- https://doi.org/10.1371/journal.pone.0006049
Abstract
Tbx1 is a T-box transcription factor implicated in DiGeorge syndrome. The molecular function of Tbx1 is unclear although it can transactivate reporters with T-box binding elements. We discovered that Tbx1 binds Smad1 and suppresses the Bmp4/Smad1 signaling. Tbx1 interferes with Smad1 to Smad4 binding, and a mutation of Tbx1 that abolishes transactivation, does not affect Smad1 binding nor does affect the ability to suppress Smad1 activity. In addition, a disease-associated mutation of TBX1 that does not prevent transactivation, prevents the TBX1-SMAD1 interaction. Expression of Tbx1 in transgenic mice generates phenotypes similar to those associated with loss of a Bmp receptor. One phenotype could be rescued by transgenic Smad1 expression. Our data indicate that Tbx1 interferes with Bmp/Smad1 signaling and provide strong evidence that a T-box transcription factor has functions unrelated to transactivation.Keywords
This publication has 36 references indexed in Scilit:
- Chordin Is a Modifier of Tbx1 for the Craniofacial Malformations of 22q11 Deletion Syndrome Phenotypes in MousePLoS Genetics, 2009
- Gain of function of Tbx1 affects pharyngeal and heart development in the mousegenesis, 2009
- Coordinated but physically separable interaction with H3K27-demethylase and H3K4-methyltransferase activities are required for T-box protein-mediated activation of developmental gene expressionGenes & Development, 2008
- Identification of downstream genetic pathways of Tbx1 in the second heart fieldDevelopmental Biology, 2008
- Human TBX1 Missense Mutations Cause Gain of Function Resulting in the Same Phenotype as 22q11.2 DeletionsAmerican Journal of Human Genetics, 2007
- An Nkx2-5/Bmp2/Smad1 Negative Feedback Loop Controls Heart Progenitor Specification and ProliferationCell, 2007
- Mesodermal expression ofTbx1is necessary and sufficient for pharyngeal arch and cardiac outflow tract developmentDevelopment, 2006
- Required, tissue-specific roles for Fgf8 in outflow tract formation and remodelingDevelopment, 2006
- Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: Implications for 22q11 deletion syndromeProceedings of the National Academy of Sciences, 2006
- Tbx1has a dual role in the morphogenesis of the cardiac outflow tractDevelopment, 2004