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bioRxiv · 10.1101/2020.01.08.898429

Conserved and divergent features of DNA methylation in embryonic stem cell-derived neurons

Martin, S.·Poppe, D.·Olova, N.·O'Leary, C.·Ivanova, E.·Pflueger, J.·Dechka, J.·Simmons, R. K.·Cooper, H. M.·Reik, W.·Lister, R.·Wolvetang, E. J.
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Abstract

DNA methylation functions in genome regulation and is implicated in neuronal maturation. Early post-natal accumulation of atypical non-CG methylation (mCH) occurs in neurons of mice and humans, but its precise function remains unknown. Here we investigate mCH deposition in neurons derived from mouse ES-cells in vitro and in cultured primary mouse neurons. We find that both acquire comparable levels of mCH over a similar period as in vivo. In vitro mCH deposition occurs concurrently with a transient increase in Dnmt3a expression, is preceded by expression of the post-mitotic neuronal marker Rbfox3 (NeuN) and is enriched at the nuclear lamina. Despite these similarities, whole genome bisulfite sequencing reveals that mCH patterning in mESC-derived neurons partially differs from in vivo. mESC-derived neurons therefore represent a valuable model system for analyzing the mechanisms and functional consequences of correct and aberrantly deposited CG and non-CG methylation in neuronal maturation.

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Martin, S., Poppe, D., Olova, N., O'Leary, C., Ivanova, E., Pflueger, J., Dechka, J., Simmons, R. K., Cooper, H. M., Reik, W., Lister, R., Wolvetang, E. J.. 2020-01-09. Conserved and divergent features of DNA methylation in embryonic stem cell-derived neurons. https://doi.org/10.1101/2020.01.08.898429

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