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Negative regulation of hypoxic responses via induced Reptin methylation.

Molecular cell | Jul 9, 2010

http://www.ncbi.nlm.nih.gov/pubmed/20603076

Lysine methylation within histones is crucial for transcriptional regulation and thus links chromatin states to biological outcomes. Although recent studies have extended lysine methylation to nonhistone proteins, underlying molecular mechanisms such as the upstream signaling cascade that induces lysine methylation and downstream target genes modulated by this modification have not been elucidated. Here, we show that Reptin, a chromatin-remodeling factor, is methylated at lysine 67 in hypoxic conditions by the methyltransferase G9a. Methylated Reptin binds to the promoters of a subset of hypoxia-responsive genes and negatively regulates transcription of these genes to modulate cellular responses to hypoxia.

Pubmed ID: 20603076 RIS Download

Mesh terms: Animals | Carrier Proteins | Cell Hypoxia | Cell Line | DNA Helicases | Female | Gene Expression Regulation, Neoplastic | Histocompatibility Antigens | Histone-Lysine N-Methyltransferase | Humans | Hypoxia-Inducible Factor 1, alpha Subunit | Lysine | Methylation | Mice | Models, Biological | Neoplasms | Oligonucleotide Array Sequence Analysis | Promoter Regions, Genetic | Protein Binding | Xenograft Model Antitumor Assays

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Associated grants

  • Agency: NIGMS NIH HHS, Id: R01 GM079641

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