PT  - JOURNAL ARTICLE
AU  - Christel Krueger
AU  - Julian R. Peat
AU  - Melanie A. Eckersley-Maslin
AU  - Timothy A. Hore
AU  - Hisham Mohammed
AU  - Simon R. Andrews
AU  - Wendy Dean
AU  - Wolf Reik
TI  - A non-catalytic role of TET3 promotes open chromatin and enhances global transcription
AID  - 10.1101/177626
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 177626
4099  - http://biorxiv.org/content/early/2017/08/17/177626.short
4100  - http://biorxiv.org/content/early/2017/08/17/177626.full
AB  - The methylcytosine dioxygenase Tet3 is highly expressed as a specific isoform in oocytes and zygotes but essentially absent from later stages of mouse preimplantation development. Here, we show that Tet3 expression promotes transdifferentiation of embryonic stem cells to trophoblast-like stem cells. By genome-wide analyses we demonstrate that TET3 associates with and co-occupies chromatin with RNA Polymerase II. Tet3 expression induces a global increase of transcription and total RNA levels, and its presence further enhances chromatin accessibility in regions open for transcription. This novel function of TET3 is not specific to the oocyte isoform, independent of its catalytic activity, the CXXC domain, or its interaction with OGT, and is localised in its highly conserved exon 4. We propose a more general role for TET3 promoting open chromatin and enhancing global transcription during changes of cellular identity, separate from its catalytic function.