Negative regulation of hypoxic responses via induced Reptin methylation.
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.
Lee
Jason S
JS
Department of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
Kim
Yunho
Y
Kim
Ik Soo
IS
Kim
Bogyou
B
Choi
Hee June
HJ
Lee
Ji Min
JM
Shin
Hi-Jai R
HJ
Kim
Jung Hwa
JH
Kim
Ji-Young
JY
Seo
Sang-Beom
SB
Lee
Ho
H
Binda
Olivier
O
Gozani
Or
O
Semenza
Gregg L
GL
Kim
Minhyung
M
Kim
Keun Il
KI
Hwang
Daehee
D
Baek
Sung Hee
SH
D000074183:ATPases Associated with Diverse Cellular Activities; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D015687:Cell Hypoxia / Q000235:genetics; D002460:Cell Line; D004265:DNA Helicases / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006649:Histocompatibility Antigens / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D023041:Xenograft Model Antitumor Assays
D002352:Carrier Proteins; D006649:Histocompatibility Antigens; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase; C525850:TIP49 protein, mouse; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C122079:RUVBL2 protein, human; D008239:Lysine