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

ABSTRACT: 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

SUBMITTER: Ziller MJ 

PROVIDER: S-EPMC6535433 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature