The thesis first describes an interesting approach for exploring locus-specific targeted DNA demethylation through Epigenetic Editing in the chapters 2&3. We targeted various potential candidates with “demethylase” activity for epigenetically silenced genes. These candidates include TET dioxygenase, cytosine deaminases, and NER pathway components. The results showed demethylation of targeted CpG sites in the ICAM-1 and EpCAM promoters for targeted TET2 and to a lesser extend for TET1. Interestingly, we also observed a small but significant increase of ICAM-1 transcription after expression of TET2CD, but not for TET2CD mutant. To our knowledge, we were the first to actually induce TET-mediated DNA demethylation at a hypermethylated site of interest, and this approach will facilitate the further studying of the mechanism of TET-induced DNA demethylation in endogenous chromatin contexts. Subsequently, in order to better understand the evolutionary history of TET dioxygenases and to provide new insights into the mechanism of DNA demethylation, we explored the catalytic properties and physiological functions of TET homologues in the more ancient organism C. reinhardtii in chapter 4. We discovered that CMD1 can catalyze 5mC to produce a novel vitamin C-derived eukaryotic DNA base modification 5gmC. We further reveal the 5gmC and its involvement in a functionally conserved but mechanistically divergent DNA demethylation pathway for the epigenetic regulation of photosynthesis. Finally, we successfully improved the mutant isolation efficiency of three low transcription level target genes in C. reinhardtii by developing a microhomology-mediated integration of donor DNA and targeted integration-dependent screening strategy in chapter 5.