title: Regulation of hypoxia-inducible gene expression after HIF activation.
abstract: Hypoxia causes dramatic changes in the expression profiles of genes that encode glycolytic enzymes, vascular endothelial growth factors, erythropoietin, and other factors in a tissue-specific manner through activating hypoxia-inducible transcription factors (HIFs) such as HIF1α and HIF2α. It has been elucidated that the activity of HIFs is fundamentally regulated by their protein stability in an oxygen-dependent manner. However, little is known about how stabilized HIFs regulate transcription of their target genes in hypoxic cells. Additionally, the roles of HIF3α, the third member of the HIFs, are still enigma due to its various splicing variants and the complicated phenotypes of Hif3a-gene modified mouse lines. Here, we summarize how molecular systems fine-tune hypoxia-inducible transcription with the cooperation of HIFs and their negative regulators, including IPAS, one of the HIF3α splicing variants. Since epigenetic mechanisms contribute to stress-inducible and cell-type specific gene regulation, the HIF-dependent reorganization of nucleosome structures in hypoxia-inducible gene promoters is also discussed.
authors.affiliation: Division of Oxygen Biology, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Cell and Molecular Biology, Karolinska Institutet, Solna, Sweden. Electronic address: sunorio@med.tohoku.ac.jp.
authors.forename: Norio
authors.initials: N
authors.lastname: Suzuki
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Solna, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Gradin
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, Solna, Sweden; Cancer Science Institute, National University of Singapore, Republic of Singapore.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Poellinger
authors.affiliation: Department of Medical Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors
keywords: Chromatin; Epigenetics; Erythropoietin; Histone; Nucleosome; Transcription