text: Many different proteins bind to particular TET enzymes and recruit the TETs to specific genomic locations.  In some studies, further analysis is needed to determine whether the interaction per se mediates the recruitment or instead the interacting partner helps to establish a favourable chromatin environment for TET binding.  TET1‑depleted and TET2‑depleted cells revealed distinct target preferences of these two enzymes, with TET1‑preferring promoters and TET2‑preferring gene bodies of highly expressed genes and enhancers.
  The three mammalian DNA methyltransferases (DNMTs) show a strong preference for adding a methyl group to the 5 carbon of a cytosine where a cytosine nucleotide is followed by a guanine nucleotide in the linear sequence of bases along its 5 → 3 direction (at CpG sites).  This forms a 5mCpG site.  More than 98% of DNA methylation occurs at CpG sites in mammalian somatic cells.  Thus TET enzymes largely initiate demethylation at 5mCpG sites.
  Oxoguanine glycosylase (OGG1) is one example of a protein that recruits a TET enzyme.  TET1 is able to act on 5mCpG if an ROS has first acted on the guanine to form  8-hydroxy-2'-deoxyguanosine (8-OHdG or its tautomer 8-oxo-dG), resulting in a 5mCp-8-OHdG dinucleotide (see Figure).  After formation of 5mCp-8-OHdG, the base excision repair enzyme OGG1 binds to the 8-OHdG lesion without immediate excision (see Figure).  Adherence of OGG1 to the 5mCp-8-OHdG site recruits TET1, allowing TET1 to oxidize the 5mC adjacent to 8-OHdG.  This initiates the demethylation pathway.
  EGR1 is another example of a protein that recruits a TET enzyme.  EGR1 has an important role in learning and memory.  When a new event such as fear conditioning causes a memory to be formed, EGR1 messenger RNA  is rapidly and selectively up-regulated in subsets of neurons in specific brain regions associated with learning and memory formation.  TET1s is the predominant isoform of TET1 that is expressed in neurons.   When EGR1 proteins are expressed, they appear to bring TET1s to about 600 sites in the neuron genome.  Then EGR1 and TET1 appear to cooperate in demethylating and thereby activating the expression of genes downstream of the EGR1 binding sites in DNA.