α-Ketoglutarate is an important metabolic intermediate that acts as a cofactor for several chromatin-modifying enzymes, including histone demethylases and the Tet family of enzymes that are involved in DNA demethylation. In this review, we focus on the function and genomic localization of these α-ketoglutarate-dependent enzymes in the maintenance of pluripotency during cellular reprogramming to induced pluripotent stem cells and in disruption of pluripotency during in vitro differentiation. The enzymatic function of many of these α-ketoglutarate-dependent proteins is required for pluripotency acquisition and maintenance. A better understanding of their specific function will be essential in furthering our knowledge of pluripotency.
Keywords: DNA demethylation; cell differentiation; cell fate; chromatin; epigenetics; histone demethylase; induced pluripotent stem cell (iPS cell) (iPSC); pluripotency; reprogramming; stem cells; α-KG enzymes.
© 2019 Tran et al.