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these conditions involve changes in gene expression. Studies of animals, isolated perfused organs, and cultured cells have demonstrated that EPO production is regulated at the transcriptional level Oz tension (reviewed in Ref. 38). An enhancer in the EPO gene 3â-flanking region is essential for modulation of transcription O2 concentration (2, 3, 5, 28, 33,40,42). EPO gene transcriptional activation is associated with expression of hypoxia-inducible factor 1 (HIF-l), which binds to the enhancer at a site required for transcription in hypoxic cells (42). activity was induced when EPO-producing Hep 3B cells and non-EPO-producing mammalian cell lines (HeLa, 293, C&, Ltk-, Chinese hamster ovary, and Rat-l) were exposed to 1% Og for 4 h (48). Analysis of genes encoding vascular endothelial growth factor (26, 27), the glycolytic enzymes aldolase A, lactate dehydrogenase A, and phosphoglycerate kinase 1 (14, 15, 41), glucose transporter 1 (lo), and inducible nitric oxide synthase (30) has identified binding sites within promoter sequences that mediate hypoxia-inducible transcription. These results provide evidence that is a general mediator of transcriptional responses to hypoxia. Induction of activity leading to EPO gene expression is a specific response to hypoxia that cannot be elicited by exposure of cells to heat shock
AJP - Cell Physiology – The American Physiological Society
Published: Oct 1, 1996
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