Negative Regulation of Hypoxic Responses via Induced Reptin Methylation

• DOI: 10.1016/j.molcel.2010.06.008
• Publication Date: 2010-07-09T08:27:59Z
• Authors: Jason S. Lee; Yunho Kim; Ik Soo Kim; Bogyou Kim; Hee June Choi; Ji Min Lee; Hi-Jai R. Shin; Jung Hwa Kim; Ji-Young Kim; Sang-Beom Seo; Ho Lee; Olivier Binda; Or Gozani; Gregg L. Semenza; Minhyung Kim; Keun Il Kim; Daehee Hwang; Sung Hee Baek
• Keywords: 0301 basic medicine; BETA; PROTEIN; Methylation; Models, Biological; CHROMATIN-REMODELING COMPLEX; Cell Line; Mice; 03 medical and health sciences; MAMMALIAN-CELLS; Histocompatibility Antigens; Neoplasms; Animals; Humans; TRANSCRIPTION; CANCER-CELLS; Promoter Regions, Genetic; Molecular Biology; INDUCIBLE FACTOR-1; GENE-EXPRESSION; Oligonucleotide Array Sequence Analysis; HISTONE H3 LYSINE-9; Lysine; DNA Helicases; Cell Biology; Histone-Lysine N-Methyltransferase; Hypoxia-Inducible Factor 1, alpha Subunit; METHYLTRANSFERASE G9A; Cell Hypoxia; Gene Expression Regulation, Neoplastic; ATPases Associated with Diverse Cellular Activities; Female; Carrier Proteins; Protein Binding

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.