Hypoxia-induced methylation of a pontin chromatin remodeling factor

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.

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Hypoxia-induced methylation of a pontin chromatin remodeling factor

机译：Hypoxia-induced methylation of a pontin chromatin remodeling factor

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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-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.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2011年第33期|13510-13515|共6页
作者
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.;
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作者单位

Department of Chemical Engineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784, South Korea;

Department of Biological Sciences, Creative Research Initiative Center for Chromatin Dynamics, Seoul National University, Seoul 151-742, South Korea;

Department of Biological Sciences, Stanford University, Stanford, CA 94305, United StatesDepartment of Biochemistry, Translational Research Center for Protein Function Control, Yonsei University, Seoul 120-749, South Korea;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Covalent nonhistone modification; Epigenetics; Transcriptional regulation;

Hypoxia-induced methylation of a pontin chromatin remodeling factor

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