title: Epigenetic regulation of hypoxia inducible factor in diseases and therapeutics.
abstract: Hypoxia-inducible factors (HIFs) are master regulators of angiogenesis and cellular adaptation in hypoxic microenvironments. Accumulating evidence indicates that HIFs also regulate cell survival, glucose metabolism, microenvironmental remodeling, cancer metastasis, and tumor progression, and thus, HIFs are viewed as therapeutic targets in many diseases. Epigenetic changes are involved in the switching 'on' and 'off' of many genes, and it has been suggested that the DNA hypermethylation of specific gene promoters, histone modifications (acetylation, phosphorylation, and methylation) and small interfering or micro RNAs be regarded epigenetic gene targets for the regulation of disease-associated cellular changes. Furthermore, the hypoxic microenvironment is one of the most important cellular stress stimuli in terms of the regulation of cellular epigenetic status via histone modification. Therefore, drug development and therapeutic approaches to ischemic diseases or cancer for targeting HIFs by modulation of epigenetic status become an attractive area. Here, the authors provide a review of the literature regarding the targeting of HIF, a key modulator of hypoxic-cell response under various disease conditions, by modulating histone or DNA using endogenous small RNAs or exogenous chemicals.
authors: School of Life Sciences and Biotechnology, College of Pharmacy, Kyungpook National University, Daegu, 702-701, Republic of Korea.
authors: Minh Phuong
authors: MP
authors: Nguyen
authors: Sangkyu
authors: S
authors: Lee
authors: You Mie
authors: YM
authors: Lee
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology* / Q000627:therapeutic use*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology; D019175:DNA Methylation / Q000187:drug effects / Q000502:physiology; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006657:Histones / Q000235:genetics; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000502:physiology / Q000627:therapeutic use; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D051793:Hypoxia-Inducible Factor 1