FIGURE 1.
TDG contains a putative PIP degron. The PIP degrons of confirmed CRL4Cdt2 substrates are shown above the putative PIP degron of TDG in human, mouse, chicken, frog, and zebrafish. TDG of lower eukaryotes, including Drosophila, does not contain a PIP box in the same region of the protein or elsewhere. Ψ, any hydrophobic residue (I/L/V/M); θ, any aromatic residue (Y/F/W). Residues shown in purple are part of the conserved PIP box, and residues shown in blue additionally contribute to the “PIP degron.” The right-hand column indicates whether each animal regulates gene expression via cytosine methylation. *, although there is some evidence of cytosine methylation in Drosophila, recent whole-genome sequencing studies suggest that the genome remains primarily unmethylated and that there are no conserved patterns of DNA methylation (65). Additionally, Drosophila lack homologs of maintenance and de novo DNA methyltransferases that are typically present in organisms that use cytosine methylation for epigenetic regulation.