Role of Activating Protein 1 in Skeletal Myogenesis

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In the proposed work we are attempting to understand the events underlying the development of cells that give rise to skeletal muscle in mammals. The commitment of cells to become specialized as muscle cells requires a particular ensemble of genes to be expressed which are required for these cells to have specialized functions such as being able to contract (allowing movement), to respond to nerve impulses from the nervous system (voluntary control of movement) and to function as a metabolic depot for the storage and combustion of energy substrates such as glucose and fats (metabolic control). In order to regulate the expression of these "muscle-specific" genes there are proteins in the nucleus called transcription factors which physically attach to and determine which genes are expressed (transcribed). These proteins function by directly binding to control regions in the DNA. In our studies we are particularly interested in a protein called Fra2 which functions in this capacity as a regulator of transcription. Our studies to date indicate that Fra2 may be an important part of a network of transcription factors controlling the formation of skeletal muscle in the embryo. Recent work has also implicated Fra2 in satellite cells which are stem cells that contribute to the repair of skeletal muscle in the adult. Our studies are thus aimed at understanding how Fra2 regulates transcription in association with other factors, and also which genes Fra2 specifically targets in the genome since only a fraction of the genes in the genome will be regulated. We will therefore use state of the art approaches in proteomics, such as mass spectrometry, to characterize the proteins that Fra2 interacts with and we will use modern approaches to genome analysis to identify the genes that Fra2 interacts with. In combination these strategies will help to elucidate the function of Fra2 protein in skeletal muscle development and post natal physiology.