title: Pathophysiological response to hypoxia - from the molecular mechanisms of malady to drug discovery: epigenetic regulation of the hypoxic response via hypoxia-inducible factor and histone modifying enzymes.
abstract: The hypoxia response regulated primarily by hypoxia-inducible factor (HIF) influences metabolism, cell survival, and angiogenesis to maintain biological homeostasis. In addition to the traditional transcriptional regulation by HIF, recent studies have shown that epigenetic modulation such as histone methylation, acetylation, and DNA methylation could change the regulation of the response to hypoxia. Eukaryotic chromatin is known to be modified by multiple post-translational histone methylation and demethylation, which result in the chromatin conformation change to adapt to hypoxic stimuli. Interestingly, some of the histone demethylase enzymes, which have the Jumonji domain-containing family, require oxygen to function and are induced by hypoxia in an HIF-1-dependent manner. Recent studies have demonstrated that histone modifiers play important roles in the hypoxic environment such as that in cancer cells and that they may become new therapeutic targets for cancer patients. It may lead to finding a new therapy for cancer to clarify a new epigenetic mechanism by HIF and histone demethylase such as JMJD1A (KDM3A) under hypoxia.
authors.affiliation: Division of Nephrology and Endocrinology, The University of Tokyo School of Medicine, Japan.
authors.forename: Imari
authors.initials: I
authors.lastname: Mimura
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Tanaka
authors.forename: Youichiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nangaku
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology; D002843:Chromatin / Q000378:metabolism; D004265:DNA Helicases / Q000502:physiology; D055808:Drug Discovery / Q000379:methods*; D044127:Epigenesis, Genetic / Q000502:physiology*; D056466:Histone Demethylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism / Q000502:physiology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D058990:Molecular Targeted Therapy / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy*; D037761:Sirtuins / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D002843:Chromatin; D006657:Histones; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D056466:Histone Demethylases; D037761:Sirtuins; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C122079:RUVBL2 protein, human