Loss of DNA methyltransferase activity in primed human ES cells triggers increased cell-cell variability and transcriptional repression.

ABSTRACT: Maintenance of pluripotency and specification towards a new cell fate are both dependent on precise interactions between extrinsic signals and transcriptional and epigenetic regulators. Directed methylation of cytosines by the de novo methyltransferases DNMT3A and DNMT3B plays an important role in facilitating proper differentiation, whereas DNMT1 is essential for maintaining global methylation levels in all cell types. Here, we generated single-cell mRNA expression data from wild-type, DNMT3A, DNMT3A/3B and DNMT1 knockout human embryonic stem cells and observed a widespread increase in cellular and transcriptional variability, even with limited changes in global methylation levels in the de novo knockouts. Furthermore, we found unexpected transcriptional repression upon eith

SUBMITTER: Tsankov AM 

PROVIDER: S-EPMC6803377 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature