Figure 6.

Model showing a simplified diagram proposing the recruitment of TET2 and DNMT3b by PU.1 to its target genes that become hypo- or hypermethylated, respectively, during osteoclastogenesis. Genes that become hypomethylated exchange PU.1-DNMT3b by PU.1-TET2 (although whether pre-existing subpopulations of these associations may exist or, alternatively, post-translational or another mechanisms may mediate exchange of TET2 and DNMT3b; this is not elucidated at present). TDG is likely to mediate conversion of 5hmC/5fmC/5caC to demethylated cytosine. Hypermethylated genes experience an increase in the binding of DNMT3b as differentiation to OCs is triggered.