Analysis of Cis‐acting Sequences Required for Operation of the Erythropoietin 3’Enhancer in Different Cell Lines a

Induction of erythropoietin (EPO) gene expression by hypoxic stimuli is a central component of the feedback system controlling erythropoiesis (for review, see refs. 1 and 2). The occurrence of rapid, high amplitude changes in gene expression3v4 in response to such a fundamental stimulus as hypoxia has focused interest on EPO as an important example of inducible gene expression. Although EPO gene expression is restricted to subpopulations of cells within liver and hypoxia induces adaptive changes in the expression of other genes in many cell types.8-10 In this paper we describe the analysis of a regulatory cis-acting sequence lying 3' to the EPO gene and provide evidence of a widespread oxygen-sensing system that interacts with specific sites within this sequence. We propose that such a system might be regulating the expression of other genes in cells not specialized for the production of erythropoietin.

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