Understanding transcription factor interactions in blood cell development

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All blood cells develop from the same parent cells, which are known as stem cells. Once the decision is made for a stem cell to develop into a particular type of blood cell, mechanisms must exist that ensure the cell only expresses the genes that are appropriate for that cell type. These mechanisms involve the action of proteins known as transcription factors, which specifically activate the expression of the correct genes. While deregulation of these control mechanisms often leads to diseases such as cancer, unfortunately our understanding of how networks of transcription factors combine to direct processes such as blood cell development is relatively poor. GATA-1 and PU.1 are essential for the normal development of erythroid and myeloid blood cell types, respectively, and the work in the present proposal is aimed at understanding some of the molecular details of how direct interactions between these two proteins modulate their activity. This information should prove useful in understanding other transcriptionally regulated systems and may eventually help provide a route to treating a number of classes of blood cancer.