| Título: | Combinatorial interactions controlling cardiac transcription |
| Autores: | Durocher, Daniel. |
| Fecha: | 1997 |
| Publicador: | McGill University - MCGILL |
| Fuente: |
 |
| Tipo: | Electronic Thesis or Dissertation |
| Tema: | Biology, Molecular. |
| Descripción: | The establishment and maintenance of the cardiac phenotype requires the activation of cardiac-specific as well as muscle-restricted genes in a tightly regulated spatial manner. This process is presumably governed by the combinatorial action of cell-restricted as well as ubiquitous transcriptional regulators. In order to unravel new cardiac transcriptional regulatory pathways and to characterize how they participate in the establishment of the cardiac transcriptional program, we used the atrial natriuretic factor (ANF) gene as a marker. This strategy led to the identification of a novel cardiac cis-element, the NKE, which is critical for the activity of the ANF promoter and which binds members of the cardiac NK2 family. The NKE is located in proximity to a critical GATA element and the phasing between these two elements is evolutionary conserved. Thus, we hypothesized that GATA-4 would functionally interact with Nkx2-5. Indeed, this work documents, for the first time, a molecular interaction between the essential cardiac proteins GATA-4 and Nkx2-5. Furthermore, this work provides a basis for GATA specificity in vitro and generates novel insights on how the cardiac genetic program is activated in early cardiogenesis. Finally, we report the cloning of a novel cardiac protein likely to have an important role in cardiogenesis, which was cloned in an effort to discover novel binding proteins that bind the critical CARE element required for high promoter activity in embryonic heart and postnatal atrium. This CARE-binding protein, CATF1, is a multifunctional helicase that defines a new family of DNA/RNA helicases. CATF1 is specifically expressed in the heart in neonates and is likely to be an activator of the ANF promoter. Collectively this work significantly furthers our knowledge on the establishment of cardiac- and chamber-specific transcription in the myocardium which is proposed here to occur via a combinatorial set of interactions among cardiac-restricted and ubiqu |
| Idioma: | en |
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