ER71 Transcriptionally Activates Brachyury: Study of Molecular Mechanisms Involved in Gene Regulation

Abstract

Congenital cardiac malformation is the most frequent birth defect which contributes to advanced heart failure in the pediatric and adult population. An enhanced understanding of the transcriptional networks that direct cardiac progenitors during heart development will have important therapeutic applications for the treatment of congenital heart disease. Furthermore, a number of parallel transcriptional pathways or networks have been proposed for the generation and regeneration of tissues such as the heart. For these reasons we predict that the definition of the transcriptional regulatory mechanisms of cardiac progenitor cells in the developing heart will enhance our understanding of cardiogenesis, congenital heart disease and myocardial regeneration. Previously, using transcriptome and RT-PCR analysis we found that ER71 was dysregulated in Nkx2-5 null embryos at both E8.0 and E9.5 in comparison to their WT littermates. This data established that ER71 is a direct downstream target of the homoedomain protein Nkx2-5. Here, we will focus on transcriptional regulation of cardiogenesis by Nkx 2.5, Etsrp71, and Brachyury (T protein).