title: Hypoxia-induced methylation of a pontin chromatin remodeling factor.
abstract: Pontin is a chromatin remodeling factor that possesses both ATPase and DNA helicase activities. Although Pontin is frequently overexpressed in human cancers of various types and implicated in oncogenic functions, the upstream signaling network leading to the regulation of Pontin that in turn affects transcription of downstream target genes has not been extensively studied. Here, we identify Pontin is methylated by G9a/GLP methyltransferases in hypoxic condition and potentiates HIF-1α-mediated activation by increasing the recruitment of p300 coactivator to a subset of HIF-1α target promoters. Intriguingly, Pontin methylation results in the increased invasive and migratory properties by activating downstream target gene, Ets1. In contrast, inhibition of Pontin methylation results in the suppression of tumorigenic and metastatic properties. Together, our data provide new approaches by targeting Pontin methylation and its downstream targets for the development of therapeutic agents for human cancers.
authors.affiliation: Department of Biological Sciences, Creative Research Initiative Center for Chromatin Dynamics, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Lee
authors.forename: Yunho
authors.initials: Y
authors.lastname: Kim
authors.forename: Jinhyuk
authors.initials: J
authors.lastname: Bhin
authors.forename: Hi-Jai R
authors.initials: HJ
authors.lastname: Shin
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Nam
authors.forename: Seung Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Jong-Bok
authors.initials: JB
authors.lastname: Yoon
authors.forename: Olivier
authors.initials: O
authors.lastname: Binda
authors.forename: Or
authors.initials: O
authors.lastname: Gozani
authors.forename: Daehee
authors.initials: D
authors.lastname: Hwang
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Baek
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D002352:Carrier Proteins / Q000378:metabolism*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D004265:DNA Helicases / Q000378:metabolism*; D057890:Epigenomics; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D002352:Carrier Proteins; D002843:Chromatin; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins; D008780:Methyltransferases; D000074183:ATPases Associated with Diverse Cellular Activities; D004265:DNA Helicases; C486549:RUVBL1 protein, human