Activation and inactivation of genes determining hemoglobin types.20s

Globin gene switching in sheep and goats has been used as a model system for examining gene expression in differentiating red blood cells. Sheep and goats switch from the synthesis of hemoglobin A to hemoglobin C in response to erythropoietin. The regulatory mechanism producing this switch in hemoglobin types could occur at the cellular, nuclear, or cytoplasmic level. Evidence is presented which suggests that regulation is occurring, in fact, at the nuclear level. Sheep and goat erythroid colonies have been grown in plasma clot culture in order to study the synthesis of individual globin chains. Erythropoietin is required for colony formation. The switch from hemoglobin A to hemoglobin C synthesis requires not only colony formation but also a higher concentration of erythropoietin than is required just for the production of colonies. A cell-free transcriptional system using bone marrow chromatin and mammalian DNA-dependent RNA polymerase has been developed in order to examine the nuclear control mechanisms in more detail.