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.
Highlights
► Reptin is a target of G9a methyltransferase ► Reptin K67 methylation is induced by hypoxia ► Genome-wide identification of hypoxia target genes negatively regulated by Reptin ► Hypoxia-driven Reptin methylation negatively regulates tumorigenic behavior in vivo
