Biochemical characterization of the developmental stage- and tissue-specific erythroid transcription factor, NF-E4

Analysis of the nuclear factors responsible for erythroid gene regulation has led to the cloning of several transcriptional regulatory proteins with clear lines of evidence suggesting or demonstrating their roles in tissue-specific gene expression. However, the erythroid cell lineage-restricted proteins that have been characterized to date do not differ significantly in activity during the distinct developmental stages of erythropoiesis, a characteristic that might be expected for a nuclear factor that actively participates in the differential regulation of various alpha- or beta-type globin genes (called globin gene switching) at distinct stages of embryonic development. We reported previously the identification of such a differentially expressed DNA binding activity, which appeared to be present in mature definitive (adult) erythroid cells but absent in immature definitive or primitive (embryonic) erythroid cells. Here we detail the biochemical properties of this erythroid tissue- and developmental stage-specific DNA binding activity (called nuclear factor-erythroid 4; NF-E4), which contains characteristics of a molecule that may be intimately involved in globin gene switching.