Egr-l, EGR2, and EGR3 are early response genes, meaning that they are rapidly and transiently stimulated by mitogens, growth factors, and a variety of other stimuli. They are also zinc finger containing transcription factors which bind specifically to the sequence GCGGGGCG, a specificity which is shared by two related factors, NGF1-C, and the product of the Wilm's tumor locus, WT33. There is evidence to suggest that egr-l is involved in establishing and maintaining differentiated function in cardiac muscle and I neural cell types. The goals of this research project are: 1) To determine whether the expression of egr-like transcription factors are critical to growth control and differentiation and to identify potential target genes. 2) To determine the function of particular protein domains of egr-l. 3) To characterize and determine the function of post-translational modifications of egr-l. Results obtained in these experiments should help elucidate how differentiation pathways are determined and how differentiated function of certain tissues is maintained. This research should also lead to a greater understanding of the egr family of transcriptional regulators. If awarded, the proposed grant will support and maintain a research effort at Meharry Medical College focused on the field of transcriptional regulation. This will broaden the available opportunities for training minority students in the Biochemistry Department. The formal relationship proposed with Dr. Daryl Granner of Vanderbilt University will afford reciprocal training opportunities and technology transfer between the two schools.
