N-methyladenine DNA Modification in Glioblastoma | Zendy

Qi Xie | Zendy; Tao Wu | Zendy; Ryan C. Gimple | Zendy; Zheng Li | Zendy; Briana C. Prager | Zendy; Qiulian Wu | Zendy; Yang Yu | Zendy; Pengcheng Wang | Zendy; Yinsheng Wang | Zendy; David U. Gorkin | Zendy; Cheng Zhang | Zendy; Alexis Dowiak | Zendy; Kaixuan Lin | Zendy; Chun Zeng | Zendy; Yinghui Sui | Zendy; Leo J.Y. Kim | Zendy; Tyler E. Miller | Zendy; Li Jiang | Zendy; Christine Lee | Zendy; Zhi Huang | Zendy; Xiaoguang Fang | Zendy; Kui Zhai | Zendy; Stephen C. Mack | Zendy; Maike Sander | Zendy; Shideng Bao | Zendy; Amber Kerstetter-Fogle | Zendy; Andrew E. Sloan | Zendy; Andrew Xiao | Zendy; Jeremy N. Rich | Zendy

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N-methyladenine DNA Modification in Glioblastoma

Author(s) -

Qi Xie,

Tao Wu,

Ryan C. Gimple,

Zheng Li,

Briana C. Prager,

Qiulian Wu,

Yang Yu,

Pengcheng Wang,

Yinsheng Wang,

David U. Gorkin,

Cheng Zhang,

Alexis Dowiak,

Kaixuan Lin,

Chun Zeng,

Yinghui Sui,

Leo J.Y. Kim,

Tyler E. Miller,

Li Jiang,

Christine Lee,

Zhi Huang,

Xiaoguang Fang,

Kui Zhai,

Stephen C. Mack,

Maike Sander,

Shideng Bao,

Amber Kerstetter-Fogle,

Andrew E. Sloan,

Andrew Xiao,

Jeremy N. Rich

Publication year - 2018

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2018.10.006

Subject(s) - biology , epigenetics , dna methylation , demethylase , histone , chromatin , cancer epigenetics , heterochromatin , dna , dna demethylation , cancer research , epigenomics , dna damage , genetics , microbiology and biotechnology , gene expression , gene , histone methyltransferase

Genetic drivers of cancer can be dysregulated through epigenetic modifications of DNA. Although the critical role of DNA 5-methylcytosine (5mC) in the regulation of transcription is recognized, the functions of other non-canonical DNA modifications remain obscure. Here, we report the identification of novel N 6 -methyladenine (N 6 -mA) DNA modifications in human tissues and implicate this epigenetic mark in human disease, specifically the highly malignant brain cancer glioblastoma. Glioblastoma markedly upregulated N 6 -mA levels, which co-localized with heterochromatic histone modifications, predominantly H3K9me3. N 6 -mA levels were dynamically regulated by the DNA demethylase ALKBH1, depletion of which led to transcriptional silencing of oncogenic pathways through decreasing chromatin accessibility. Targeting the N 6 -mA regulator ALKBH1 in patient-derived human glioblastoma models inhibited tumor cell proliferation and extended the survival of tumor-bearing mice, supporting this novel DNA modification as a potential therapeutic target for glioblastoma. Collectively, our results uncover a novel epigenetic node in cancer through the DNA modification N 6 -mA.

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