Tets are susceptible to competitive inhibition by fumarate and succinate, resulting in lower global 5-hmC levels in cells treated with cell-permeable forms of these compounds.
A and B, IC50 curves of Tet1 and Tet2 for fumarate and succinate, respectively. C and D, HPLC-MS/MS quantitation of global 5-hmC (C) and 5-mC (D) levels in SK-N-BE(2) cells incubated with increasing concentrations of diethyl fumarate or dimethyl succinate for 48 h (n ≥ 3). 5-hmC and 5-mC quantitation graphs represent mean ± S.E. *, p < 0.05.