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Hypoxia-induced methylation of a pontin chromatin remodeling factor

Lookup NU author(s): Dr Jo Lee, Dr Olivier Binda

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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.


Publication metadata

Author(s): Lee JS, Kim Y, Bhin J, Shin HJ, Nam HJ, Lee SH, Yoon JB, Binda O, Gozani O, Hwang D, Baek SH

Publication type: Article

Publication status: Published

Journal: PNAS

Year: 2011

Volume: 108

Issue: 33

Pages: 13510-13515

Print publication date: 08/08/2011

ISSN (print): 0027-8424

ISSN (electronic): 1091-6490

Publisher: National Academy of Sciences

URL: http://www.pnas.org/content/108/33/13510.long

DOI: 10.1073/pnas.1106106108

PubMed id: 21825155


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