OGT binds a conserved C-terminal domain of TET1 to regulate TET1 activity and function in development

Joel Hrit, Leeanne Goodrich, Cheng Li, Bang An Wang, Ji Nie, Xiaolong Cui, Elizabeth Allene Martin, Eric Simental, Jenna Fernandez, Monica Yun Liu, Joseph R. Nery, Rosa Castanon, Rahul M. Kohli, Natalia Tretyakova, Chuan He, Joseph R. Ecker, Mary Goll, Barbara Panning

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43 Scopus citations


TET enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine and higher oxidized derivatives. TETs stably associate with and are post-translationally modified by the nutrient-sensing enzyme OGT, suggesting a connection between metabolism and the epigenome. Here, we show for the first time that modification by OGT enhances TET1 activity in vitro. We identify a TET1 domain that is necessary and sufficient for binding to OGT and report a point mutation that disrupts the TET1-OGT interaction. We show that this interaction is necessary for TET1 to rescue hematopoetic stem cell production in tet mutant zebrafish embryos, suggesting that OGT promotes TET1’s function during development. Finally, we show that disrupting the TET1-OGT interaction in mouse embryonic stem cells changes the abundance of TET2 and 5-methylcytosine, which is accompanied by alterations in gene expression. These results link metabolism and epigenetic control, which may be relevant to the developmental and disease processes regulated by these two enzymes.

Original languageEnglish (US)
Article numbere34870
StatePublished - Oct 2018

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