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A Gro/TLE-NuRD corepressor complex facilitates Tbx20-dependent transcriptional repression
Erin Kaltenbrun1, Todd M Greco, Christopher E Slagle
1Departments of Biology and ‡Genetics, University of North Carolina , Chapel Hill, North Carolina 27599, United States.
Journal of Proteome Research
|September 13, 2013
Summary
The cardiac transcription factor Tbx20 forms repressor complexes with TLE/Groucho proteins and the NuRD complex. This interaction is crucial for regulating gene expression during embryonic heart development.
Area of Science:
- Molecular Biology
- Developmental Biology
- Genetics
Background:
- The cardiac transcription factor Tbx20 is essential for vertebrate heart development.
- Misregulation of Tbx20 is linked to congenital heart disease.
- The precise mechanisms of Tbx20-mediated transcriptional regulation are not fully understood.
Purpose of the Study:
- To characterize the protein complexes associated with Tbx20.
- To elucidate how Tbx20 mediates transcriptional regulation in the embryonic heart.
- To identify the functional significance of Tbx20-protein interactions in heart development.
Main Methods:
- Immunoaffinity purification of tagged Tbx20 followed by proteomic analysis (GeLC-MS/MS).
- Gene ontology classification and functional network analysis of identified proteins.
- In vivo studies involving motif ablation and validation in mouse embryonic hearts.
Main Results:
- Tbx20 associates with a chromatin remodeling network including TLE/Groucho corepressors, NuRD complex, RUVBL1/RUVBL2, and Tbx18.
- Interaction with TLE corepressors is mediated by an eh1 binding motif in Tbx20.
- Ablation of the eh1 motif disrupts Tbx20 function and repressor complex assembly in vivo.
- Tbx20-TLE interactions were validated in mouse embryonic hearts, identifying regulated developmental genes.
Conclusions:
- Tbx20 functions by associating with a TLE/Groucho-NuRD repressor complex.
- This Tbx20-TLE repressor complex plays a critical role in preventing inappropriate gene activation during embryonic heart development.
- The findings provide a model for Tbx20-mediated transcriptional repression in cardiac morphogenesis.
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