Abstract
Hypoxia or reduced oxygen availability has been studied extensively for its ability to activate specific genes. Hypoxia-induced gene expression is mediated by the HIF transcription factors, but not exclusively so. Despite the extensive knowledge about how hypoxia activates genes, much less is known about how hypoxia promotes gene repression. In this review, we discuss the potential mechanisms underlying hypoxia-induced transcriptional repression responses. We highlight HIF-dependent and independent mechanisms as well as the potential roles of dioxygenases with functions at the nucleosome and DNA level. Lastly, we discuss recent evidence regarding the involvement of transcriptional repressor complexes in hypoxia.
Highlights
Decreases in oxygen availability are generally called hypoxia
Chromatin accessibility is one of the major determinants of Hypoxia Inducible Factor (HIF) binding, but not the only one. This provides a potential explanation for the differential genome-wide HIF binding profile and gene expression patterns in response to hypoxia observed across cell lines
Through the use of proteomics, use of proteomics, this study identified an increase in Heterochromatin Protein 1 Binding Protein this study identified an increase in Heterochromatin Protein 1 Binding Protein 3 (HP1BP3) in
Summary
Decreases in oxygen availability are generally called hypoxia. These can occur at the organism level such as when climbing high mountains or at the cellular level when oxygen supply is reduced and/or metabolic activity is high [1,2,3]. To achieve a cellular response to hypoxia, cells have evolved mechanisms that impinge at all levels of gene expression regulation [2,5] and energy conservation processes. These involve blocks in translation and the cell cycle and switches in metabolic processes such as moving from oxidative phosphorylation to glycolysis [2]. Chromatin accessibility is one of the major determinants of HIF binding, but not the only one This provides a potential explanation for the differential genome-wide HIF binding profile and gene expression patterns in response to hypoxia observed across cell lines. Chromatin should be considered an important player in the cellular response to hypoxia
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