Reprogramming of DNA methylation at NEUROD2-bound sequences during cortical 
neuron differentiation

Hahn, M. A.; Jin, S.-G.; Li, A. X.; Liu, J.; Huang, Z.; Wu, X.; Kim, B.-W.; Johnson, J.; Bilbao, A.-D. V.; Tao, S.; Yim, J. A.; Fong, Y.; Goebbels, S.; Schwab, M. H.; Lu, Q.; Pfeifer, G. P.

doi:10.1126/sciadv.aax0080

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Reprogramming of DNA methylation at NEUROD2-bound sequences during cortical neuron differentiation

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Goebbels, S.
Developmental neurobiology, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

/persons/resource/persons182402

Schwab, M. H.
Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

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引用

Hahn, M. A., Jin, S.-G., Li, A. X., Liu, J., Huang, Z., Wu, X., Kim, B.-W., Johnson, J., Bilbao, A.-D.-V., Tao, S., Yim, J. A., Fong, Y., Goebbels, S., Schwab, M. H., Lu, Q., & Pfeifer, G. P. (2019). Reprogramming of DNA methylation at NEUROD2-bound sequences during cortical neuron differentiation. Science Advances, 5(10):. doi:10.1126/sciadv.aax0080.

引用: https://hdl.handle.net/21.11116/0000-000A-CD4B-C

要旨

The characteristics of DNA methylation changes that occur during neurogenesis in vivo remain unknown.
We used whole-genome bisulfite sequencing to quantitate DNA cytosine modifications in differentiating
neurons and their progenitors isolated from mouse brain at the peak of embryonic neurogenesis. Localized
DNA hypomethylation was much more common than hypermethylation and often occurred at putative
enhancers within genes that were upregulated in neurons and encoded proteins crucial for neuronal differ-
entiation. The hypomethylated regions strongly overlapped with mapped binding sites of the key neuronal
transcription factor NEUROD2. The 5-methylcytosine oxidase ten-eleven translocation 2 (TET2) interacted
with NEUROD2, and its reaction product 5-hydroxymethylcytosine accumulated at the demethylated
regions. NEUROD2-targeted differentially methylated regions retained higher methylation levels in Neurod2
knockout mice, and inducible expression of NEUROD2 caused TET2-associated demethylation at its in vivo
binding sites. The data suggest that the reorganization of DNA methylation in developing neurons involves
NEUROD2 and TET2-mediated DNA demethylation.