The research proposal explores the regulation of c-myb expression. c-myb expression is required for the correct development of hematopoietic cells; aberrant expression prevents normal blood cell differentiation, resulting in leukemias and lymphomas. In hematopoietic tissues, c-myb expression is high during early stages of development, and is subsequently down- regulated due to a transcriptional attenuation mechanism, presumably mediated by DNA-binding proteins. A single DNA-binding activity that correlates with c-myb expression in B cells, this protein will be identified, purified, and tested for biological activity. In parallel, the protein factors and DNA elements that control c-myb expression in IL2-stimulated T cells, during erythroid differentiation , will likewise by characterized. These systems will help define the role of c-myb regulatory proteins during a number of biologically-relevant conditions in which the level of c-myb transcripts change. As several critical regulatory genes (such as c- fos and c-myc) are also regulated at the level of transcription elongation, these experiments may elucidate a global regulatory mechanism governing the expression of a number of such genes.
