GSE32268
Role of DNMT3B in the regulation of early neural and neural crest specifiers
The de novo DNA methyltransferase DNMT3B functions in establishing DNA methylation patterns during development. We performed RNAi knockdown of DNMT3B in human embryonic stem cells (ESCs) in order to investigate the mechanistic contribution of DNMT3B on DNA methylation and early neuronal differentiation.  Genome-wide analyses of DNA methylation by MethylC-seq identified novel regions of hypomethylation in the DNMT3B knockdowns along the X chromosome as well as pericentromeric regions, rather than changes to specific dysregulated gene promoters.  While DNMT3B was not required for early neuroepithelium specification, DNMT3B deficient neuroepithelium exhibited accelerated maturation with earlier expression of mature neuronal markers (such as NEUROD1) and early neuronal regional specifiers (such as neural crest) relative to normal ESCs. Our results suggest that DNMT3B mediates large-scale methylation patterns in human ESCs and that DNMT3B deficiency alters the timing of neuronal maturational differentiation in human neuronal cultures. Overall design: Examined DNA methylation in human embryonic stem cells, both with and without DNMT3B knockdown