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lüll 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 Mimura I; Tanaka T; Wada Y; Kodama T; Nangaku MJ Pharmacol Sci 2011[]; 115 (4): 453-8The 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.|ATPases Associated with Diverse Cellular Activities[MESH]|Animals[MESH]|Carrier Proteins/physiology[MESH]|Chromatin/metabolism[MESH]|DNA Helicases/physiology[MESH]|Drug Discovery/*methods[MESH]|Epigenesis, Genetic/*physiology[MESH]|Histone Demethylases/metabolism[MESH]|Histones/*metabolism[MESH]|Humans[MESH]|Hypoxia-Inducible Factor 1, alpha Subunit/metabolism/*physiology[MESH]|Hypoxia-Inducible Factor 1/metabolism/*physiology[MESH]|Hypoxia/genetics/*metabolism[MESH]|Models, Biological[MESH]|Molecular Targeted Therapy/methods[MESH]|Neoplasms/*drug therapy[MESH]|Sirtuins/physiology[MESH] |