Phosphorylation of the retinoic acid receptor RARgamma2 is crucial for the neuronal differentiation of mouse embryonic stem cells - Archive ouverte HAL Access content directly
Journal Articles Journal of Cell Science Year : 2014

Phosphorylation of the retinoic acid receptor RARgamma2 is crucial for the neuronal differentiation of mouse embryonic stem cells

Abstract

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.

Dates and versions

hal-04143706 , version 1 (29-06-2023)

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Ziad Al Tanoury, Samia Gaouar, Aleksandr Piskunov, Tao Ye, Sylvia Urban, et al.. Phosphorylation of the retinoic acid receptor RARgamma2 is crucial for the neuronal differentiation of mouse embryonic stem cells. Journal of Cell Science, 2014, 127 (Pt 9), pp.2095-2105. ⟨10.1242/jcs.145979⟩. ⟨hal-04143706⟩
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