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

5-Hydroxymethylcytosine Epigenome
DOI: 10.7554/elife.34870 Publication Date: 2018-10-16T12:01:30Z
ABSTRACT
TET enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine and higher oxidized derivatives. TETs stably associate with are post-translationally modified by the nutrient-sensing enzyme OGT, suggesting a connection between metabolism epigenome. Here, we show for first time that modification OGT enhances TET1 activity in vitro. We identify domain is necessary sufficient binding report point mutation disrupts TET1-OGT interaction. this interaction rescue hematopoetic stem cell production tet mutant zebrafish embryos, promotes TET1’s function during development. Finally, disrupting mouse embryonic cells changes abundance of TET2 5-methylcytosine, which accompanied alterations gene expression. These results link epigenetic control, may be relevant developmental disease processes regulated these two enzymes.
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