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

Sally Martin, Daniel Poppe, Nelly Olova, Conor O'Leary, Elena Ivanova, Jahnvi Pflueger, Jennifer Dechka, Rebecca K. Simmons, Helen M. Cooper, Wolf Reik, Ryan Lister, Ernst Wolvetang

Research output: Contribution to journalArticle

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.
Original languageEnglish
Article number898429
Number of pages61
JournalbioRxiv
Volume2020
Issue number01.08
DOIs
Publication statusPublished - 9 Jan 2020

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DNA Methylation
Embryonic Stem Cells
Neurons
Methylation
Nuclear Lamina
Genome
Mouse Embryonic Stem Cells
In Vitro Techniques

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Martin, Sally ; Poppe, Daniel ; Olova, Nelly ; O'Leary, Conor ; Ivanova, Elena ; Pflueger, Jahnvi ; Dechka, Jennifer ; Simmons, Rebecca K. ; Cooper, Helen M. ; Reik, Wolf ; Lister, Ryan ; Wolvetang, Ernst. / Conserved and divergent features of DNA methylation in embryonic stem cell-derived neurons. In: bioRxiv. 2020 ; Vol. 2020, No. 01.08.
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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, RK, Cooper, HM, Reik, W, Lister, R & Wolvetang, E 2020, 'Conserved and divergent features of DNA methylation in embryonic stem cell-derived neurons' bioRxiv, vol. 2020, no. 01.08, 898429. https://doi.org/10.1101/2020.01.08.898429

Conserved and divergent features of DNA methylation in embryonic stem cell-derived neurons. / Martin, Sally; Poppe, Daniel; Olova, Nelly; O'Leary, Conor; Ivanova, Elena; Pflueger, Jahnvi; Dechka, Jennifer; Simmons, Rebecca K.; Cooper, Helen M.; Reik, Wolf; Lister, Ryan; Wolvetang, Ernst.

In: bioRxiv, Vol. 2020, No. 01.08, 898429, 09.01.2020.

Research output: Contribution to journalArticle

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AU - Lister, Ryan

AU - Wolvetang, Ernst

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AB - 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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