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 specialist publicationArticle

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
Number of pages61
Volume2020
No.01.08
Specialist publicationbioRxiv
DOIs
Publication statusPublished - 9 Jan 2020

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