Deutsch
 
Benutzerhandbuch Datenschutzhinweis Impressum Kontakt
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT

Freigegeben

Zeitschriftenartikel

Dissecting the Functional Consequences of De Novo DNA Methylation Dynamics in Human Motor Neuron Differentiation and Physiology

MPG-Autoren
/persons/resource/persons203772

Galonska,  Christina
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons203770

Meissner,  Alexander
Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society;

Externe Ressourcen
Es sind keine Externen Ressourcen verfügbar
Volltexte (frei zugänglich)

Ziller.pdf
(Verlagsversion), 6MB

Ergänzendes Material (frei zugänglich)
Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar
Zitation

Ziller, M. J., Ortega, J. A., Quinlan, K. A., Santos, D. P., Gu, H., Martin, E. J., et al. (2018). Dissecting the Functional Consequences of De Novo DNA Methylation Dynamics in Human Motor Neuron Differentiation and Physiology. Cell Stem Cell, 22, 1-16. doi:10.1016/j.stem.2018.02.012.


Zitierlink: http://hdl.handle.net/21.11116/0000-0000-DFEB-D
Zusammenfassung
The somatic DNA methylation (DNAme) landscape is established early in development but remains highly dynamic within focal regions that overlap with gene regulatory elements. The significance of these dynamic changes, particularly in the central nervous system, remains unresolved. Here, we utilize a powerful human embryonic stem cell differentiation model for the generation of motor neurons (MNs) in combination with genetic mutations in the de novo DNAme machinery. We quantitatively dissect the role of DNAme in directing somatic cell fate with high-resolution genome-wide bisulfite-, bulk-, and single-cell-RNA sequencing. We find defects in neuralization and MN differentiation in DNMT3A knockouts (KO) that can be rescued by the targeting of DNAme to key developmental loci using catalytically inactive dCas9. We also find decreased dendritic arborization and altered electrophysiological properties in DNMT3A KO MNs. Our work provides a list of DNMT3A-regulated targets and a mechanistic link between de novo DNAme, cellular differentiation, and human MN function.