Our understanding of the transcriptional regulation of cardiac development has improved greatly over the last decade, as many transcriptional regulators important for heart morphogenesis have been identified and characterized. It is also becoming clear that many of these regulators recruit a host of other protein cofactors that modulate gene expression in a cardiac specific fashion. One such family of transcriptional modulators important for cardiac development is the Friend of GATA (FOG) family. Both members of the FOG family have been shown to be expressed in the heart, interact with GATA factors, and be required for normal heart development. In this proposal, we demonstrate that both members of the FOG transcriptional modulator family contain a repression domain localized to their N-terminus that physically interacts with subunits of a large chromatin remodeling complex called the NuRD complex. Given their important role in gene regulation, it is not surprising that chromatin remodeling complexes might also be very important in regulating events during embryonic development. In this proposal, we outline research to further characterize these FOG/NuRD interactions and demonstrate their importance for mammalian cardiac development. Specifically, we propose to (1) characterize the subunits of the NuRD complex that interact with the FOG repression motif during cardiac development, (2) determine the functional significance of FOG-2/NuRD interactions during cardiac development, and (3) determine the functional significance of FOG-I/NURD interactions during cardiac development. The results of this work will lead to new insights into the transcriptional regulation of heart development, and may lead to a better understanding of the molecular basis of congenital and acquired heart disease. ? ? ?
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