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DNA N6-methyladenine is dynamically regulated in the mouse brain following environmental stress.

ABSTRACT: Chemical modifications on DNA molecules, such as 5-methylcytosine and 5-hydroxymethylcytosine, play important roles in the mammalian brain. A novel DNA adenine modification, N(6)-methyladenine (6mA), has recently been found in mammalian cells. However, the presence and function(s) of 6mA in the mammalian brain remain unclear. Here we demonstrate 6mA dynamics in the mouse brain in response to environmental stress. We find that overall 6mA levels are significantly elevated upon stress. Genome-wide 6mA and transcriptome profiling reveal an inverse association between 6mA dynamic changes and a set of upregulated neuronal genes or downregulated LINE transposon expression. Genes bearing stress-induced 6mA changes significantly overlap with loci associated with neuropsychiatric disorders. These results suggest an epigenetic role for 6mA in the mammalian brain as well as its potential involvement in neuropsychiatric disorders.

SUBMITTER: Yao B

PROVIDER: S-EPMC5654764 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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DNA N6-methyladenine is dynamically regulated in the mouse brain following environmental stress.

Yao Bing B Cheng Ying Y Wang Zhiqin Z Li Yujing Y Chen Li L Huang Luoxiu L Zhang Wenxin W Chen Dahua D Wu Hao H Tang Beisha B Jin Peng P

Nature communications 20171024 1

Chemical modifications on DNA molecules, such as 5-methylcytosine and 5-hydroxymethylcytosine, play important roles in the mammalian brain. A novel DNA adenine modification, N(6)-methyladenine (6mA), has recently been found in mammalian cells. However, the presence and function(s) of 6mA in the mammalian brain remain unclear. Here we demonstrate 6mA dynamics in the mouse brain in response to environmental stress. We find that overall 6mA levels are significantly elevated upon stress. Genome-wide ...[more]

PMID: 29066820

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Project description:BackgroundIn recent years, the prevalence of Alzheimer's disease (AD) has increased, which places a great burden on society and families and creates considerable challenges for medical services. N6-methyladenine (m6A) deoxyribonucleic acid (DNA) adenine methylation is a novel biomarker and is abundant in the brain, but less common in AD. We support to analyze the relationship between DNA m6A and cognition in patients with AD and normal controls (NCs) in China.AimTo analyze the relationship between the novel m6A DNA and cognition in patients with AD and NCs in China.MethodsA total of 179 AD patients (mean age 71.60 ± 9.89 years; males: 91; females: 88) and 147 NCs (mean age 69.59 ± 11.22 years; males: 77; females: 70) who were age- and sex-matched were included in our study. All subjects underwent neuropsychological scale assessment and magnetic resonance imaging examination. Apolipoprotein E (APOE) genotypes were measured through agarose gel electrophoresis. Global m6A levels were evaluated by a MethylFlash m6A DNA Methylation ELISA Kit (colorimetric). Global m6A levels in total DNA from ten AD patients with 18F-AV-45 (florbetapir) positron emission tomography (PET) positivity and ten NCs with PET negativity were analyzed by dot blotting to determine the results.ResultsOur ELISA results showed that the global m6A DNA levels in peripheral blood were different between patients with AD and NCs (P = 0.002; < 0.05). And ten AD patients who were PET positive and ten NCs who were PET negative also showed the same results through dot blotting. There were significant differences between the two groups, which indicated that the leukocyte m6A DNA levels were different (P = 0.005; < 0.05). The m6A level was approximately 8.33% lower in AD patients than in NCs (mean 0.011 ± 0.006 vs 0.012 ± 0.005). A significant correlation was found between the Montreal Cognitive Assessment score and the peripheral blood m6A level in the tested population (r = 0.143, P = 0.01; < 0.05). However, no relationship was found with APOE ε4 (P = 0.633, > 0.05). Further studies should be performed to validate these findings.ConclusionOur results show that reduced global m6A DNA methylation levels are significantly lower in AD patients than in NCs by approximately 8.33% in China.

Dataset Information

DNA N6-methyladenine is dynamically regulated in the mouse brain following environmental stress.

Publications

DNA N6-methyladenine is dynamically regulated in the mouse brain following environmental stress.

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