First Author | Al Tanoury Z | Year | 2014 |
Journal | J Cell Sci | Volume | 127 |
Issue | Pt 9 | Pages | 2095-105 |
PubMed ID | 24569880 | Mgi Jnum | J:213065 |
Mgi Id | MGI:5582844 | Doi | 10.1242/jcs.145979 |
Citation | Al Tanoury Z, et al. (2014) Phosphorylation of the retinoic acid receptor RARgamma2 is crucial for the neuronal differentiation of mouse embryonic stem cells. J Cell Sci 127(Pt 9):2095-105 |
abstractText | Retinoic acid (RA) plays key roles in cell differentiation and growth arrest by activating nuclear RA receptors (RARs) (alpha, beta and gamma), which are ligand-dependent transcription factors. RARs are also phosphorylated in response to RA. Here, we investigated the in vivo relevance of the phosphorylation of RARs during RA-induced neuronal differentiation of mouse embryonic stem cells (mESCs). Using ESCs where the genes encoding each RAR subtype had been inactivated, and stable rescue lines expressing RARs mutated in phospho-acceptor sites, we show that RA-induced neuronal differentiation involves RARgamma2 and requires RARgamma2 phosphorylation. By gene expression profiling, we found that the phosphorylated form of RARgamma2 regulates a small subset of genes through binding an unusual RA response element consisting of two direct repeats with a seven-base-pair spacer. These new findings suggest an important role for RARgamma phosphorylation during cell differentiation and pave the way for further investigations during embryonic development. |