N⁶-methyladenine DNA Modification in Glioblastoma.

ABSTRACT: 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 N⁶-methyladenine (N⁶-mA) DNA modifications in human tissues and implicate this epigenetic mark in human disease, specifically the highly malignant brain cancer glioblastoma. Glioblastoma markedly upregulated N⁶-mA levels, which co-localized with heterochromatic histone modifications, predominantly H3K9me3. N⁶-mA levels were dynamically regulated by the DNA demethylase ALKBH1, depletion of which led to transcriptional silencing of oncogenic pat

SUBMITTER: Xie Q 

PROVIDER: S-EPMC6433469 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature