title: The regulation of transcriptional repression in hypoxia.
abstract: A sufficient supply molecular oxygen is essential for the maintenance of physiologic metabolism and bioenergetic homeostasis for most metazoans. For this reason, mechanisms have evolved for eukaryotic cells to adapt to conditions where oxygen demand exceeds supply (hypoxia). These mechanisms rely on the modification of pre-existing proteins, translational arrest and transcriptional changes. The hypoxia inducible factor (HIF; a master regulator of gene induction in response to hypoxia) is responsible for the majority of induced gene expression in hypoxia. However, much less is known about the mechanism(s) responsible for gene repression, an essential part of the adaptive transcriptional response. Hypoxia-induced gene repression leads to a reduction in energy demanding processes and the redirection of limited energetic resources to essential housekeeping functions. Recent developments have underscored the importance of transcriptional repressors in cellular adaptation to hypoxia. To date, at least ten distinct transcriptional repressors have been reported to demonstrate sensitivity to hypoxia. Central among these is the Repressor Element-1 Silencing Transcription factor (REST), which regulates over 200 genes. In this review, written to honor the memory and outstanding scientific legacy of Lorenz Poellinger, we provide an overview of our existing knowledge with respect to transcriptional repressors and their target genes in hypoxia.
authors.affiliation: Instituto Gulbenkian de Ciência, Rua da Quinta Grande, 2780-156 Oeiras, Portugal.
authors.forename: Miguel A S
authors.initials: MAS
authors.lastname: Cavadas
authors.affiliation: Life and Health Sciences, Aston University, Birmingham B4 7ET, UK.
authors.forename: Alex
authors.initials: A
authors.lastname: Cheong
authors.affiliation: Systems Biology Ireland, University College Dublin, Dublin 4, Ireland; Conway Institute of Biomolecular and Biomedical Research, School of Medicine and Medical Sciences and Systems Biology Ireland, University College Dublin, Dublin 4, Ireland. Electronic address: cormac.taylor@ucd.ie.
authors.forename: Cormac T
authors.initials: CT
authors.lastname: Taylor
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010100:Oxygen
keywords: Hypoxia; REST; Repressor; Transcription