Identification of a CD4 Promoter Binding Protein with a CD4-Specific Binding Pattern.  Students will combine biology and chemistry techniques to identify and characterize transcription factors controlling thymocyte differentiation During T cell development in the thymus CD4-helper and CD8-killer T cells arise from a common thymocyte precursor. A complex pattern of CD4 regulation, primarily controlled by the activity of the CD4 silencer, allows CD4 gene expression in the developing CD4-helper T cells and, at the same time, silences CD4 expression in thymocytes that develop into CD8-killer T cells. However, CD4 silencer activity is not sufficient to determine CD-4 helper cell fate, indicating that there are additional differences in regulation of CD4 expression between CD4 and CD8 cells that may elucidate how “killer” vs. “helper” transcriptional regulatory programs are established and maintained. We have observed a CD4 promoter binding activity that is present in nuclear extracts of CD4, but not CD8 cells, which could explain the differences in CD4 gene expression in the two T cell types. Current projects focus on purifying this candidate transcription factor using a biochemical approach.