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

• DOI: 10.7554/elife.34870
• Publication Date: 2018-10-16T12:01:30Z
• Authors: Joel Hrit; Leeanne Goodrich; Cheng Li; Bang-An Wang; Ji Nie; Xiaolong Cui; Elizabeth Allene ...; 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
• Keywords: 5-Hydroxymethylcytosine; Epigenome

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.