Helmholtz Gemeinschaft


DAZL regulates Tet1 translation in murine embryonic stem cells

Item Type:Article
Title:DAZL regulates Tet1 translation in murine embryonic stem cells
Creators Name:Welling, M. and Chen, H.H. and Muñoz, J. and Musheev, M.U. and Kester, L. and Junker, J.P. and Mischerikow, N. and Arbab, M. and Kuijk, E. and Silberstein, L. and Kharchenko, P.V. and Geens, M. and Niehrs, C. and van de Velde, H. and van Oudenaarden, A. and Heck, A.J. and Geijsen, N.
Abstract:Embryonic stem cell (ESC) cultures display a heterogeneous gene expression profile, ranging from a pristine naïve pluripotent state to a primed epiblast state. Addition of inhibitors of GSK3β and MEK (so-called 2i conditions) pushes ESC cultures toward a more homogeneous naive pluripotent state, but the molecular underpinnings of this naïve transition are not completely understood. Here, we demonstrate that DAZL, an RNA-binding protein known to play a key role in germ-cell development, marks a subpopulation of ESCs that is actively transitioning toward naive pluripotency. Moreover, DAZL plays an essential role in the active reprogramming of cytosine methylation. We demonstrate that DAZL associates with mRNA of Tet1, a catalyst of 5-hydroxylation of methyl-cytosine, and enhances Tet1 mRNA translation. Overexpression of DAZL in heterogeneous ESC cultures results in elevated TET1 protein levels as well as increased global hydroxymethylation. Conversely, null mutation of Dazl severely stunts 2i-mediated TET1 induction and hydroxymethylation. Our results provide insight into the regulation of the acquisition of naïve pluripotency and demonstrate that DAZL enhances TET1-mediated cytosine hydroxymethylation in ESCs that are actively reprogramming to a pluripotent ground state.
Keywords:2 i Conditions, Dazl, DNA Hydroxymethylation, Naive Pluripotency, TET 1, Animals, Mice
Source:EMBO Reports
Publisher:EMBO Press / Wiley
Page Range:791-802
Date:July 2015
Official Publication:https://doi.org/10.15252/embr.201540538
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library