Critical roles of protein methyltransferases and demethylases in the regulation of embryonic stem cell fate.

Accumulating evidence has recently shown that protein methyltransferases and demethylases are crucial regulators in either maintaining pluripotent states or inducing differentiation of embryonic stem cells. These enzymes control pluripotent signatures by mediating activation or repression of histone marks, or through direct methylation of non-histone proteins. Importantly, chromatin modifiers can influence the fate of many differentiation-related genes by loosening chromatin and allowing for transcriptional activation of lineage-specific genes. Genome-wide studies have unraveled diverse changes in methylation patterns following embryonic stem cell differentiation, with redistribution of heterochromatic and euchromatic marks, underlying the importance of chromatin modifiers in governing the fate of embryonic stemness. Furthermore, the development of small molecule inhibitors targeting these agents may shed light in potential clinical implementation to reprogram embryonic stem cells for biomedical therapeutics. Ever since the pioneering introduction of induced pluripotent stem cells, the challenge for application in regenerative medicine and broader medical therapeutics has commenced.