Tet1 strongly binds to unmethylated-CpG rich regions (such as gene promoters, CGIs) via its CXXC domain, limiting the accessibility of DNMTs. Tet1 also binds to dispersedly methylated-CpGs in euchromatin (shown as green nucleosomes) and converts 5mC to 5hmC. The newly generated 5hmC may further limit the binding of methyl-binding proteins (MBDs) or DNMTs. However, densely-methylated CpGs can recruit MBDs, which subsequently recruits repressive histone modifiers such as H3K9me3 methyltransferases to establish a heterochromatin state (shown as dark blue nucleosomes), making Tet1 inaccessible to these hypermethylated sites and preventing the conversion from 5mC to 5hmC. Arrow denotes the gene promoter. Please refer to the related text for more details.