Physiology meets biophysics: Visualizing the interaction of hypoxia-inducible factor 1α with p300 and CBP

Complex circulatory and respiratory systems are established during embryonic development and used in fetal and postnatal life to ensure oxygen delivery to every cell in the human body. Within each cell, the utilization of O2 as a substrate for biochemical reactions, most notably as an electron acceptor in the mitochondria, is also highly regulated. As a result of systemic and cellular physiological mechanisms that control O2 delivery and consumption, O2 concentrations are precisely maintained within a narrow range that represents a balance between cellular metabolic requirements and the risk of oxidative damage. Since its identification ten years ago (1), an exponentially growing body of experimental data indicates that the transcription factor hypoxia-inducible factor 1 (HIF-1) functions as a global regulator of O2 homeostasis, as it is required for the establishment of the circulatory and respiratory systems as well as for physiological responses to hypoxia in prenatal and postnatal life (2–7).