Stress-induced accumulation of DNA N6-Methyladenine in prefrontal cortex

ABSTRACT: Chemical covalent modifications on the 5-carbon position of cytosine, such as 5- methylcytosine and 5-hydroxymethylcytosine, are a set of well-characterized epigenetic marks that shape transcriptional landscaping. Compiling evidence suggests central roles of cytosine modification dynamics in neuronal functions such as memory formation and stress response. N6-methyladenine (6mA) that previously described in bacteria has been recently found in higher eukaryotes, including worms, flies and mice. However, the precise roles and molecular mechanisms of 6mA in mammalian genome, particularly CNS, remain vague. Here we report that the global 6mA level is elevated in mice prefrontal cortex (PFC) upon restraint stress. The 6mA dynamics responding to stress is independent of Tet1 and Tet2 proteins, whose Drosophila ortholog serves as a 6mA demethylase. Genome-wide 6mA profiling in control and stressed PFC reveal that 6mA dynamic changes upon stress predominantly occur on intragenic introns and repetitive elements. Global transcriptome analyzes indicate a set of upregulated genes bearing elevated 6mA levels are highly enriched in neuronal pathways response to stress, suggesting a positive correlation of 6mA with transcription of these loci. In addition, 6mA dynamics in stress response could also influence transposon expression. Furthermore, 6mA is depleted in cortex enhancers, indicating their cis-regulatory roles in transcription. Motif identifications using 6mA dynamic regions provide putative transcription factors and epigenetic modulators binding sites with mechanistic hints. Taken together, our findings reveal dynamic 6mA changes in mice PFC in response to stress, and define its potential epigenetic roles in modulating gene and transposon expression.

ORGANISM(S): Mus musculus

PROVIDER: GSE79543 | GEO | 2017/10/24

SECONDARY ACCESSION(S): PRJNA316141

REPOSITORIES: GEO