Hypoxia-induced methylation of a pontin chromatin remodeling factor

Jason S. Lee, Yunho Kim, Jinhyuk Bhin, Hi Jai R. Shin, Hye Jin Nam, Seung Hoon Lee, Jong Bok Yoon, Olivier Binda, Or Gozani, Daehee Hwang, Sung Hee Baek

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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.

Original languageEnglish
Pages (from-to)13510-13515
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number33
DOIs
Publication statusPublished - 2011 Aug 16

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All Science Journal Classification (ASJC) codes

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Lee, J. S., Kim, Y., Bhin, J., Shin, H. J. R., Nam, H. J., Lee, S. H., Yoon, J. B., Binda, O., Gozani, O., Hwang, D., & Baek, S. H. (2011). Hypoxia-induced methylation of a pontin chromatin remodeling factor. Proceedings of the National Academy of Sciences of the United States of America, 108(33), 13510-13515. https://doi.org/10.1073/pnas.1106106108