Abstract
Oxygen sensing is an essential feature of metazoan biology and reductions in oxygen availability (hypoxia) have both physiological and pathophysiological implications. Co-ordinated mechanisms have evolved for sensing and responding to hypoxia, which involve diverse biological outputs, with the main aim of restoring oxygen homeostasis. This includes a dynamic gene transcriptional response, the central drivers of which are the hypoxia-inducible factor (HIF) family of transcription factors. HIFs are regulated in an oxygen-dependent manner and while their role in hypoxia is well established, it is apparent that other key players are required for gene expression control in hypoxia. In this review, we highlight the current understanding of the known and potential molecular mechanisms underpinning gene transcriptional responses to hypoxia in mammals, with a focus on oxygen-dependent effects on chromatin structure.
Highlights
Molecular oxygen is a co-factor in various biochemical reactions and is essential for many aerobic organisms in their maintenance of intracellular ATP levels [1]
Changes in gene expression are at the forefront of cellular responses to hypoxia, with the transcription factor family hypoxia inducible factor (HIF) as a master regulator
Very recently, chromatin epigenetic marks have been shown to be essential for gene expression changes in hypoxia as well as cellular fate
Summary
Molecular oxygen is a co-factor in various biochemical reactions and is essential for many aerobic organisms in their maintenance of intracellular ATP levels [1]. Mechanisms of chromatin regulation in low oxygen will be essential to better understanding hypoxia in normal physiological responses and disease.
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