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Gene regulation in response to graded hypoxia: The non-redundant roles of the oxygen sensors and FIH in the HIF pathway by Frédéric Dayan; Marc Monticelli; Jacques Pouysségur; Elisabeth Pécou is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is Gene regulation in response to graded hypoxia: The non-redundant roles of the oxygen sensors and FIH in the HIF pathway about?

Hypoxia Inducible Factor (HIF), being the master protein involved in adaptation to low pO 2 , plays a major role in many physiological and pathological phenomena: development, inflammation, ischemia and cancer. Prolyl hydroxylase (PHD) and factor inhibiting HIF (FIH) are the two oxygen sensors that regulate the HIF pathway. Here we model the regulatory dynamics in an oxygen gradient by a system of differential equations. A part of the work consists in a qualitative analysis, driven independently of the values of the parameters, which explains the non-redundant functional roles of FIH and PHD. In a second part, we use biological experiments to fit the model in a physiologically relevant context and run simulations. Simulation results are confronted with success to independent biological experiments. The combination of biological data and mathematical analysis stresses that FIH is a fine modulator determining whether a given gene should be induced in mildly or in strongly hypoxic areas. Moreover it gives access to other functional predictions that are not directly accessible by pure experiments, for instance the stoichiometry of prolyl-hydroxylation on HIF, and the switch-like proper

Who reads Gene regulation in response to graded hypoxia: The non-redundant roles of the oxygen sensors and FIH in the HIF pathway?

Author

Frédéric Dayan; Marc Monticelli; Jacques Pouysségur; Elisabeth Pécou

Publisher

Elsevier Science; Elsevier ; Elsevier Inc.; Elsevier BV (ISSN 0022-5193)

Published

2009

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)