Premium
DAZL regulates Tet1 translation in murine embryonic stem cells
Author(s) -
Welling Maaike,
Chen HsuHsin,
Muñoz Javier,
Musheev Michael U,
Kester Lennart,
Junker Jan Philipp,
Mischerikow Nikolai,
Arbab Mandana,
Kuijk Ewart,
Silberstein Lev,
Kharchenko Peter V,
Geens Mieke,
Niehrs Christof,
de Velde Hilde,
Oudenaarden Alexander,
Heck Albert JR,
Geijsen Niels
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201540538
Subject(s) - embryonic stem cell , stem cell , microbiology and biotechnology , translation (biology) , biology , genetics , gene , messenger rna
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 GSK 3β and MEK (so‐called 2i conditions) pushes ESC cultures toward a more homogeneous naïve 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 ESC s that is actively transitioning toward naïve 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 TET 1 protein levels as well as increased global hydroxymethylation. Conversely, null mutation of Dazl severely stunts 2i‐mediated TET 1 induction and hydroxymethylation. Our results provide insight into the regulation of the acquisition of naïve pluripotency and demonstrate that DAZL enhances TET 1‐mediated cytosine hydroxymethylation in ESC s that are actively reprogramming to a pluripotent ground state.