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Distal and proximal hypoxia response elements cooperate to regulate organ-specific erythropoietin gene expression

Orlando, Ilaria M. C. ; Lafleur, Véronique N. ; Storti, Federica ; Spielmann, Patrick ; Crowther, Lisa ; Santambrogio, Sara ; Schödel, Johannes ; Hoogewijs, David ; Mole, David R. ; Wenger, Roland H.

In: Haematologica, 2019, vol. 105, no. 12, p. 2774–2784

While it is well-established that distal hypoxia response elements (HREs) regulate hypoxia-inducible factor (HIF) target genes such as erythropoietin (Epo), an interplay between multiple distal and proximal (promoter) HREs has not been described so far. Hepatic Epo expression is regulated by a HRE located downstream of the EPO gene, but this 3' HRE is dispensable for renal EPO gene...