Abstract:
:Retinoic acid (RA) plays key roles in cell differentiation and growth arrest by activating nuclear RA receptors (RARs) (α, β and γ), 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 RARγ2 and requires RARγ2 phosphorylation. By gene expression profiling, we found that the phosphorylated form of RARγ2 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 RARγ phosphorylation during cell differentiation and pave the way for further investigations during embryonic development.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Al Tanoury Z,Gaouar S,Piskunov A,Ye T,Urban S,Jost B,Keime C,Davidson I,Dierich A,Rochette-Egly Cdoi
10.1242/jcs.145979subject
Has Abstractpub_date
2014-05-01 00:00:00pages
2095-105issue
Pt 9eissn
0021-9533issn
1477-9137pii
jcs.145979journal_volume
127pub_type
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