Fig. 6

Potential model for the role of TET3 in repeat methylation at FMR1 with an expanded CGG repeat. (a) In individuals with higher levels of TET3, the enzyme potentially functions in both a catalytic and non-catalytic role to affect methylation levels at the FMR1 CGG repeat expansion. Utilising the catalytic domain, TET3 may be directly responsible for the establishment of 5hmC at the locus. In a non-catalytic function, TET3 directly regulates DNMT1 expression which in turn is responsible for methylation at the FMR1 CGG repeat expansion. (b) In individuals with reduced TET3 levels, there is insufficient enzyme to establish and maintain high levels of 5hmC at the FMR1 promoter. The lower levels of TET3 also affect DNMT1 expression leading to a depletion in DNMT1 activity and lower levels of methylation at the FMR1 locus