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Whole genome bisulfite sequencing of mouse neural progenitor cells and neurons from the mouse cerebral cortex at day 15.5 of embryonic development

ABSTRACT: Global changes in DNA methylation occur during mammalian development but may be more limited during differentiation of cell lineages. The extent and specific nature of methylation changes at the time when neural progenitor cells in the brain cease proliferation and commit to become differentiated cortical neurons remains unknown. Here, we have used whole genome bisulfite sequencing to quantitate a level of modified bisulfite-resistant cytosines (5-methylcytosine and 5-hydroxymethylcytosine) at base resolution in differentiating neurons and their progenitors isolated from mouse brain at the peak of embryonic neurogenesis. We find that, during this transition, globally, modified cytosine pattern is very stable. Localized losses of modified cytosines (hypomethylation) were much more common than gains and were targeted frequently to intragenic enhancer regions marked by H3K27 acetylation. Most genes with intragenic clustered hypomethylated CpG sites were upregulated in neurons and encoded factors essential for neurogenesis. The hypomethylated regions were enriched in motifs recognized by the neuronal transcription factor NEUROD2 which become activated in differentiated neurons. NEUROD2 binding coincided with 80% of the hypomethylated intragenic enhancer regions. The data suggest that in developing neurons, the limited reorganization of the DNA methylome reflects the engagement of intragenic enhancers by NEUROD2 in parallel with activation of neuronal function-related genes.

ORGANISM(S): Mus musculus

PROVIDER: GSE101090 | GEO | 2017/12/31

SECONDARY ACCESSION(S): PRJNA393698

REPOSITORIES: GEO

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