C-Jun-N-terminal phosphorylation regulates DNMT1 expression and genome wide methylation in gliomas
Heiland DH, Ferrarese R, Claus R, Dai F, Masilamani AP, Kling E, Weyerbrock A, Kling T, Nelander S, Carro MS (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 8
Pages Range: 6940-6954
Journal Issue: 4
DOI: 10.18632/oncotarget.14330
Abstract
High-grade gliomas (HGG) are the most common brain tumors, with an average survival time of 14 months. A glioma-CpG island methylator phenotype (G-CIMP), associated with better clinical outcome, has been described in low and high-grade gliomas. Mutation of IDH1 is known to drive the G-CIMP status. In some cases, however, the hypermethylation phenotype is independent of IDH1 mutation, suggesting the involvement of other mechanisms. Here, we demonstrate that DNMT1 expression is higher in low-grade gliomas compared to glioblastomas and correlates with phosphorylated c-Jun. We show that phospho-c-Jun binds to the DNMT1 promoter and causes DNA hypermethylation. Phospho-c-Jun activation by Anisomycin treatment in primary glioblastoma-derived cells attenuates the aggressive features of mesenchymal glioblastomas and leads to promoter methylation and downregulation of key mesenchymal genes (CD44, MMP9 and CHI3L1). Our findings suggest that phospho-c-Jun activates an important regulatory mechanism to control DNMT1 expression and regulate global DNA methylation in Glioblastoma.
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Germany (DE)
Sweden (SE)How to cite
APA:
Heiland, D.H., Ferrarese, R., Claus, R., Dai, F., Masilamani, A.P., Kling, E.,... Carro, M.S. (2017). C-Jun-N-terminal phosphorylation regulates DNMT1 expression and genome wide methylation in gliomas. Oncotarget, 8(4), 6940-6954. https://doi.org/10.18632/oncotarget.14330
MLA:
Heiland, Dieter Henrik, et al. "C-Jun-N-terminal phosphorylation regulates DNMT1 expression and genome wide methylation in gliomas." Oncotarget 8.4 (2017): 6940-6954.
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