Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 33, Pages 13510-13515Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1106106108
Keywords
epigenetics; transcriptional regulation; covalent nonhistone modification
Categories
Funding
- Research Center for Chromatin Dynamics [2009-0081563]
- Converging Research Center [2010K001298]
- Basic Science Research Program [3344-20100053]
- National Junior Research Fellowship [NRF-2011-A01496-0001806]
- Ministry of Education, Science, and Technology (MEST) of Korea
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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-1 alpha-mediated activation by increasing the recruitment of p300 coactivator to a subset of HIF-1 alpha 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.
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