Role of hypoxia-inducible factors in epigenetic regulation via histone demethylases.

Abstract

Eukaryotic chromatin is subject to multiple posttranslational histone modifications such as acetylation, methylation, phosphorylation, and ubiquitination. These various covalent modifications have been proposed to constitute a "histone code," playing important roles in the establishment of global chromatin environments, transcription, DNA repair, and DNA replication. Among these modifications, histone methylation specifies regulatory marks that delineate transcriptionally active and inactive chromatin. These histone methyl marks were considered irreversible; however, recent identification of site-specific histone demethylases demonstrates that histone methylation is dynamically regulated, which may allow cells to rapidly change chromatin conformation to adapt to environmental stresses or intrinsic stimuli. Of major interest is the observation that these histone demethylase enzymes, which are in the Jumonji gene family, require oxygen to function and, in some cases, are induced by hypoxia in an HIFalpha-dependent manner. This provides a new mechanism for regulation of the response to hypoxia.

• Authors: Jun Yang, Ioanna Ledaki, Helen Turley, Kevin C Gatter, Juan-Carlos Martinez Montero, Ji-Liang Li, Adrian L Harris
• Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1177 Pg. 185-97 (Oct 2009) ISSN: 1749-6632 [Electronic] United States
• PMID: 19845621 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Basic Helix-Loop-Helix Transcription Factors
• DNA-Binding Proteins
• Jumonji Domain-Containing Histone Demethylases
• Kdm5b protein, mouse
• Retinoblastoma-Binding Protein 2
• Oxidoreductases, N-Demethylating

Topics

• Animals
• Basic Helix-Loop-Helix Transcription Factors (genetics, metabolism, physiology)
• DNA-Binding Proteins
• Epigenesis, Genetic
• Gene Expression Regulation
• Humans
• Jumonji Domain-Containing Histone Demethylases
• Mice
• Oxidoreductases, N-Demethylating (classification, genetics, metabolism)
• Phylogeny
• Retinoblastoma-Binding Protein 2