Hypoxia, Erythropoietin Gene Expression, and Erythropoiesis

The sections in this article are: 1 The Functional Anatomy of the Erythropoietin Molecule 1 The Erythropoietin Receptor 2 Erythropoiesis and Erythroid Differentiation 3 Modulation of Serum Erythropoietin Levels 3.1 Assays for Erythropoietin 3.2 Serum Erythropoietin Levels and Their Dependence on Oxygenation 3.3 Kinetics and Quantity of Increases in Serum Erythropoietin Levels 3.4 Disturbances in Oxygen-Dependent Control of Serum Erythropoietin Levels 3.5 Clearance and Metabolic Fate of Erythropoietin 4 The Source of Erythropoietin 4.1 Organs Producing Erythropoietin 4.2 Relative Contribution of Liver and Kidneys to Erythropoietin Formation 4.3 Cellular Site of Erythropoietin Formation 5 Oxygen Sensing in the Control of Erythropoietin Formation 5.1 Evidence for Intrarenal Oxygen Sensing 5.2 The Role of Local Oxygenation in Hepatic Erythropoietin Formation 5.3 The Role of Local Oxygenation for Renal Erythropoietin Formation 5.4 Mechanism of Oxygen Sensing and Signal Transduction 6 Control of Erythropoietin Gene Expression 6.1 Modulation of Erythropoietin mRNA Levels 6.2 Cis-Acting Sequences that Coordinate Gene Expression 6.3 Sequence Conservation in Erythropoietin Genes 6.4 Hypersensitive Sites in Erythropoietin Genes 6.5 The Promoter of the Erythropoietin Gene 6.6 Enhancer Elements 3′ to the Erythropoietin Gene 6.7 Operation of Distant Cis-Acting Elements to Control Tissue Specificity of Gene Expression 6.8 Cis-Acting Sequences in Erythropoietin mRNA 7 Relationship to other Adaptive Responses to Hypoxia