TET Genes: new players in DNA demethylation and important determinants for stemness  Fabian Mohr, Konstanze Döhner, Christian Buske, Vijay P.S. Rawat  Experimental Hematology  Volume 39, Issue 3, Pages 272-281 (March 2011) DOI: 10.1016/j.exphem.2010.12.004 Copyright © 2011 ISEH - Society for Hematology and Stem Cells Terms and Conditions

Figure 1 Schematic overview of TET proteins (A) including functional relevant domains and sequences. (B) Schematic overview of TET gene alignment and homology of the protein sequence. The Cys-rich domain (CD) and double-stranded ß-helix-2OG-Fe(II)-dependent dioxygenase domain (DSBH) show three peaks in homology (indicated by red box). Experimental Hematology 2011 39, 272-281DOI: (10.1016/j.exphem.2010.12.004) Copyright © 2011 ISEH - Society for Hematology and Stem Cells Terms and Conditions

Figure 2 Enzymatic conversion of cytosine to 5-hydroxymethylcytosine. DNA-methyl-transferases convert cytosine to 5-methylcytosine, which in mouse and human subsequently is converted by TET proteins to 5-hydroxymethylcytosine. Experimental Hematology 2011 39, 272-281DOI: (10.1016/j.exphem.2010.12.004) Copyright © 2011 ISEH - Society for Hematology and Stem Cells Terms and Conditions

Figure 3 Function of Tet1 in murine ES cell maintenance. Tet1 facilitates ES cell maintenance, resulting in a demethylated Nanog promoter and self-renewal. Knockdown of Tet1 leads to hypermethylation of the Nanog promoter and subsequently to a decrease in Nanog expression. Further, upregulation of markers related to differentiation is observed and the ES cells differentiate phenotypically. Experimental Hematology 2011 39, 272-281DOI: (10.1016/j.exphem.2010.12.004) Copyright © 2011 ISEH - Society for Hematology and Stem Cells Terms and Conditions

Figure 4 Missense, nonsense, and frameshift mutations of TET2 in myeloid disorders. While nonsense and frameshift mutations are scattered throughout the whole sequence, in the homology-peak regions of the TET family mainly missense mutations are found. This indicates alterations in functionally important domains of TET2 and relates to the reported clonal expansion of TET2 mutant cell populations in patients. Adapted from [18,21,35,38,40–42,44,45,47–48]. Experimental Hematology 2011 39, 272-281DOI: (10.1016/j.exphem.2010.12.004) Copyright © 2011 ISEH - Society for Hematology and Stem Cells Terms and Conditions