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J Proteome Res
2013 Dec 06;1212:5395-409. doi: 10.1021/pr400818c.
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A Gro/TLE-NuRD corepressor complex facilitates Tbx20-dependent transcriptional repression.
Kaltenbrun E
,
Greco TM
,
Slagle CE
,
Kennedy LM
,
Li T
,
Cristea IM
,
Conlon FL
.
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The cardiac transcription factor Tbx20 has a critical role in the proper morphogenetic development of the vertebrate heart, and its misregulation has been implicated in human congenital heart disease. Although it is established that Tbx20 exerts its function in the embryonic heart through positive and negative regulation of distinct gene programs, it is unclear how Tbx20 mediates proper transcriptional regulation of its target genes. Here, using a combinatorial proteomic and bioinformatic approach, we present the first characterization of Tbx20 transcriptional protein complexes. We have systematically investigated Tbx20 protein-protein interactions by immunoaffinity purification of tagged Tbx20 followed by proteomic analysis using GeLC-MS/MS, gene ontology classification, and functional network analysis. We demonstrate that Tbx20 is associated with a chromatin remodeling network composed of TLE/Groucho corepressors, members of the Nucleosome Remodeling and Deacetylase (NuRD) complex, the chromatin remodeling ATPases RUVBL1/RUVBL2, and the T-box repressor Tbx18. We determined that the interaction with TLE corepressors is mediated via an eh1 binding motif in Tbx20. Moreover, we demonstrated that ablation of this motif results in a failure to properly assemble the repression network and disrupts Tbx20 function in vivo. Importantly, we validated Tbx20-TLE interactions in the mouse embryonic heart, and identified developmental genes regulated by Tbx20-TLE binding, thereby confirming a primary role for a Tbx20-TLE repressor complex in embryonic heart development. Together, these studies suggest a model in which Tbx20 associates with a Gro/TLE-NuRD repressor complex to prevent inappropriate gene activation within the forming heart.
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Ahn,
tbx20, a new vertebrate T-box gene expressed in the cranial motor neurons and developing cardiovascular structures in zebrafish.
2000, Pubmed
Ahn,
tbx20, a new vertebrate T-box gene expressed in the cranial motor neurons and developing cardiovascular structures in zebrafish.
2000,
Pubmed
Amin,
RNA-seq in the tetraploid Xenopus laevis enables genome-wide insight in a classic developmental biology model organism.
2014,
Pubmed
,
Xenbase
Bindea,
ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks.
2009,
Pubmed
Bowen,
Mi-2/NuRD: multiple complexes for many purposes.
2004,
Pubmed
Brown,
Developmental expression of the Xenopus laevis Tbx20 orthologue.
2003,
Pubmed
,
Xenbase
Brown,
Tbx5 and Tbx20 act synergistically to control vertebrate heart morphogenesis.
2005,
Pubmed
,
Xenbase
Buscarlet,
The 'Marx' of Groucho on development and disease.
2007,
Pubmed
Buscarlet,
Cofactor-activated phosphorylation is required for inhibition of cortical neuron differentiation by Groucho/TLE1.
2009,
Pubmed
Cai,
T-box genes coordinate regional rates of proliferation and regional specification during cardiogenesis.
2005,
Pubmed
Cai,
Tbx20 acts upstream of Wnt signaling to regulate endocardial cushion formation and valve remodeling during mouse cardiogenesis.
2013,
Pubmed
Cai,
YY1 functions with INO80 to activate transcription.
2007,
Pubmed
Chakraborty,
Tbx20 regulation of cardiac cell proliferation and lineage specialization during embryonic and fetal development in vivo.
2012,
Pubmed
Chen,
A functional interaction between the histone deacetylase Rpd3 and the corepressor groucho in Drosophila development.
1999,
Pubmed
Choi,
The homeodomain protein NK-3 recruits Groucho and a histone deacetylase complex to repress transcription.
1999,
Pubmed
Christoffels,
Formation of the venous pole of the heart from an Nkx2-5-negative precursor population requires Tbx18.
2006,
Pubmed
Christoffels,
Tbx18 and the fate of epicardial progenitors.
2009,
Pubmed
Cinnamon,
Context-dependent regulation of Groucho/TLE-mediated repression.
2008,
Pubmed
Cox,
MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification.
2008,
Pubmed
Cristea,
Fluorescent proteins as proteomic probes.
2005,
Pubmed
Eden,
GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists.
2009,
Pubmed
Farin,
Transcriptional repression by the T-box proteins Tbx18 and Tbx15 depends on Groucho corepressors.
2007,
Pubmed
Ford,
A SWI/SNF- and INO80-dependent nucleosome movement at the INO1 promoter.
2007,
Pubmed
Formaz-Preston,
The Tbx20 homolog Midline represses wingless in conjunction with Groucho during the maintenance of segment polarity.
2012,
Pubmed
Fujita,
MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte differentiation.
2004,
Pubmed
Gaunt,
Homoeobox gene expression in mouse embryos varies with position by the primitive streak stage.
,
Pubmed
Goetz,
TBX5 is required for embryonic cardiac cell cycle progression.
2006,
Pubmed
,
Xenbase
Greco,
Nuclear import of histone deacetylase 5 by requisite nuclear localization signal phosphorylation.
2011,
Pubmed
Griffin,
A conserved role for H15-related T-box transcription factors in zebrafish and Drosophila heart formation.
2000,
Pubmed
Hammer,
Characterization of TBX20 in human hearts and its regulation by TFAP2.
2008,
Pubmed
Hang,
Chromatin regulation by Brg1 underlies heart muscle development and disease.
2010,
Pubmed
Hendrich,
Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development.
2001,
Pubmed
Huang,
C/EBP transcription factors mediate epicardial activation during heart development and injury.
2012,
Pubmed
Iio,
Expression pattern of novel chick T-box gene, Tbx20.
2001,
Pubmed
Ikura,
Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis.
2000,
Pubmed
Jin,
A mammalian chromatin remodeling complex with similarities to the yeast INO80 complex.
2005,
Pubmed
Joshi,
The functional interactome landscape of the human histone deacetylase family.
2013,
Pubmed
Kaltenbrun,
Xenopus: An emerging model for studying congenital heart disease.
2011,
Pubmed
,
Xenbase
Kirk,
Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy.
2007,
Pubmed
Klopf,
Cooperation between the INO80 complex and histone chaperones determines adaptation of stress gene transcription in the yeast Saccharomyces cerevisiae.
2009,
Pubmed
Kraus,
Cloning and expression analysis of the mouse T-box gene Tbx18.
2001,
Pubmed
Langmead,
Fast gapped-read alignment with Bowtie 2.
2012,
Pubmed
Li,
C23 interacts with B23, a putative nucleolar-localization-signal-binding protein.
1996,
Pubmed
Li,
The Sequence Alignment/Map format and SAMtools.
2009,
Pubmed
Li,
ZIP: a novel transcription repressor, represses EGFR oncogene and suppresses breast carcinogenesis.
2009,
Pubmed
Liu,
T-box transcription factor TBX20 mutations in Chinese patients with congenital heart disease.
2008,
Pubmed
Mandel,
The BMP pathway acts to directly regulate Tbx20 in the developing heart.
2010,
Pubmed
,
Xenbase
Marino,
Mutants in the mouse NuRD/Mi2 component P66alpha are embryonic lethal.
2007,
Pubmed
Meins,
Characterization of the human TBX20 gene, a new member of the T-Box gene family closely related to the Drosophila H15 gene.
2000,
Pubmed
Miteva,
Proteomics-based methods for discovery, quantification, and validation of protein-protein interactions.
2013,
Pubmed
Montgomery,
Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility.
2007,
Pubmed
Nie,
SIX1 acts synergistically with TBX18 in mediating ureteral smooth muscle formation.
2010,
Pubmed
Olson,
Homeodomain-mediated beta-catenin-dependent switching events dictate cell-lineage determination.
2006,
Pubmed
Qian,
Transcription factor neuromancer/TBX20 is required for cardiac function in Drosophila with implications for human heart disease.
2008,
Pubmed
Reller,
Prevalence of congenital heart defects in metropolitan Atlanta, 1998-2005.
2008,
Pubmed
Roche,
The zinc finger and C-terminal domains of MTA proteins are required for FOG-2-mediated transcriptional repression via the NuRD complex.
2008,
Pubmed
Rottbauer,
Reptin and pontin antagonistically regulate heart growth in zebrafish embryos.
2002,
Pubmed
Sakabe,
Dual transcriptional activator and repressor roles of TBX20 regulate adult cardiac structure and function.
2012,
Pubmed
Santisteban,
Dynamic expression of Groucho-related genes Grg1 and Grg3 in foregut endoderm and antagonism of differentiation.
2010,
Pubmed
Sardiu,
Probabilistic assembly of human protein interaction networks from label-free quantitative proteomics.
2008,
Pubmed
Shen,
Tbx20 regulates a genetic program essential to adult mouse cardiomyocyte function.
2011,
Pubmed
Shen,
A chromatin remodelling complex involved in transcription and DNA processing.
2000,
Pubmed
Singh,
Tbx20 is essential for cardiac chamber differentiation and repression of Tbx2.
2005,
Pubmed
Smith,
Dorsalization and neural induction: properties of the organizer in Xenopus laevis.
1983,
Pubmed
,
Xenbase
Smoot,
Cytoscape 2.8: new features for data integration and network visualization.
2011,
Pubmed
Stennard,
Cardiac T-box factor Tbx20 directly interacts with Nkx2-5, GATA4, and GATA5 in regulation of gene expression in the developing heart.
2003,
Pubmed
,
Xenbase
Stennard,
Murine T-box transcription factor Tbx20 acts as a repressor during heart development, and is essential for adult heart integrity, function and adaptation.
2005,
Pubmed
Szklarczyk,
The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored.
2011,
Pubmed
Takeuchi,
Tbx20 dose-dependently regulates transcription factor networks required for mouse heart and motoneuron development.
2005,
Pubmed
Tandon,
Tcf21 regulates the specification and maturation of proepicardial cells.
2013,
Pubmed
,
Xenbase
Trapnell,
Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation.
2010,
Pubmed
Tsai,
Functional proteomics establishes the interaction of SIRT7 with chromatin remodeling complexes and expands its role in regulation of RNA polymerase I transcription.
2012,
Pubmed
Villanueva,
TLE3 is a dual-function transcriptional coregulator of adipogenesis.
2011,
Pubmed
Wang,
PaxDb, a database of protein abundance averages across all three domains of life.
2012,
Pubmed
Xue,
NURD, a novel complex with both ATP-dependent chromatin-remodeling and histone deacetylase activities.
1998,
Pubmed
Yochum,
Pf1, a novel PHD zinc finger protein that links the TLE corepressor to the mSin3A-histone deacetylase complex.
2001,
Pubmed
Zeng,
Developmental patterns and characteristics of epicardial cell markers Tbx18 and Wt1 in murine embryonic heart.
2011,
Pubmed
Zybailov,
Quantitative shotgun proteomics using a protease with broad specificity and normalized spectral abundance factors.
2007,
Pubmed
van der Linde,
Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis.
2011,
Pubmed
