TET genes: new players in DNA demethylation and important determinants for stemness

Stem cells are defined as cells that have the ability to perpetuate themselves through self-renewal and to generate functional mature cells by differentiation. During each stage, coordinated gene expression is crucial to maintain the balance between self-renewal and differentiation. Disturbance of this accurately balanced system can lead to a variety of malignant disorders. In mammals, DNA cytosine-5 methylation is a well-studied epigenetic pathway that is catalyzed by DNA methyltransferases and is implicated in the control of balanced gene expression, but also in hematological malignancies. In this review, we focus on the TET (ten-eleven-translocation) genes, which recently were identified to catalyze the conversion of cytosine-5 methylation to 5-hydroxymethyl-cytosine, an intermediate form potentially involved in demethylation. In addition, members of the TET family are playing a role in ES cell maintenance and inner cell mass cell specification and were demonstrated to be involved in hematological malignancies. Recently, a correlation between low genomic 5-hydroxymethyl-cytosine and TET2 mutation status was shown in patients with myeloid malignancies.