Biology subjects

Goll, M.

Publications and source records attributed to Goll, M..

2 recordsLinked to original sources

bioRxiv2018

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

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 domain of TET1 responsible for binding to OGT and report a point mutation that disrupts the TET1-OGT interaction. We show that the TET1-OGT interaction is necessary for TET1 to rescue hematopoetic stem cell production in tet mutant zebrafish embryos, suggesting that OGT promotes TET1s function during development. Finally, we show that disrupting the TET1-OGT interaction in mouse embryonic stem cells changes the abundance of TET-containing high molecular weight complexes and causes widespread gene expression changes. These results link metabolism and epigenetic control, which may be relevant to the developmental and disease processes regulated by these two enzymes.

biochemistry↗

bioRxiv2017

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

Mammalian TET enzymes oxidize 5-methylcytosine to 5-hydroxymethylcytosine and higher oxidized derivatives. TETs are targets of the enzyme OGT, which post-translationally modifies intracellular proteins in response to cellular nutrient status. The biological implications of the OGT-TET interaction have not been thoroughly explored. Here, we show for the first time that modification of TET1 by OGT enhances its activity in vitro. We identify a previously uncharacterized domain of TET1 responsible for binding to OGT and report a point mutation that disrupts the OGT-TET1 interaction. Finally, we show that the interaction between TET1 and OGT is necessary for TET1 to rescue tet mutant zebrafish hematopoetic stem cell formation, suggesting that OGT promotes TET1s function in development. Our results demonstrate regulation of TET activity by OGT in vitro and in vivo. These results link metabolism and epigenetic control, which may be relevant to the developmental and disease processes regulated by these two enzymes.

biochemistry↗