OGT Binds a Conserved C-terminal Domain of TET1 to Regulate TET1 Activity and Function in Development

Overview

Journal Elife

Specialty Biology

Date 2018 Oct 17

PMID 30325306

Citations 36

Authors

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

Affiliations

Soon will be listed here.

Abstract

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.

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