biostudies-literatureTsankov AMNIDDK NIH HHSNIAID NIH HHSNHGRI NIH HHSNIGMS NIH HHSdev174722https://www.ebi.ac.uk/biostudies/studies/S-EPMC6803377biostudies-literatureUnknown146(19)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 <i>de novo</i> 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 <i>de novo</i> knockouts. Furthermore, we found unexpected transcriptional repression upon eithDevelopment (Cambridge, England)Loss of DNA methyltransferase activity in primed human ES cells triggers increased cell-cell variability and transcriptional repression.PMC6803377DP3 DK111898U24 AI118672P01 GM099117DP2 GM119419RM1 HG006193Allon SJMeissner AAkopian VMead BEShalek AKCharlton JArczewska ATsankov AMWadsworth MHMikkelsen TSDrake RSSmith ZDfalseLoss of DNA methyltransferase activity in primed human ES cells triggers increased cell-cell variability and transcriptional repression.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 <i>de novo</i> 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 <i>de novo</i> knockouts. Furthermore, we found unexpected transcriptional repression upon eith2019-01-01T00:00:00Z2019 Sep2026-05-04T23:39:55.727Z2020-10-08T07:28:20ZS-EPMC68033773151522410.1242/dev.174722