Assessment and site-specific manipulation of DNA (hydroxy-)methylation during mouse corticogenesis

Florian Noack, Abhijeet Pataskar, Martin Schneider, Frank Buchholz, Vijay K Tiwari, Federico Calegari

Research output: Contribution to journalArticle

5 Citations (Scopus)
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Abstract

Dynamic changes in DNA (hydroxy-)methylation are fundamental for stem cell differentiation. However, the signature of these epigenetic marks in specific cell types during corticogenesis is unknown. Moreover, site-specific manipulation of cytosine modifications is needed to reveal the significance and function of these changes. Here, we report the first assessment of (hydroxy-)methylation in neural stem cells, neurogenic progenitors, and newborn neurons during mammalian corticogenesis. We found that gain in hydroxymethylation and loss in methylation occur sequentially at specific cellular transitions during neurogenic commitment. We also found that these changes predominantly occur within enhancers of neurogenic genes up-regulated during neurogenesis and target of pioneer transcription factors. We further optimized the use of dCas9-Tet1 manipulation of (hydroxy-)methylation, locus-specifically, in vivo, showing the biological relevance of our observations for Dchs1, a regulator of corticogenesis involved in developmental malformations and cognitive impairment. Together, our data reveal the dynamics of cytosine modifications in lineage-related cell types, whereby methylation is reduced and hydroxymethylation gained during the neurogenic lineage concurrently with up-regulation of pioneer transcription factors and activation of enhancers for neurogenic genes.

Original languageEnglish
Article numbere201900331
Number of pages15
JournalLife science alliance
Volume2
Issue number2
Early online date27 Feb 2019
DOIs
Publication statusPublished - Apr 2019

Bibliographical note

© 2019 Noack et al.

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