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Publication : Csn3 gene is regulated by all-trans retinoic acid during neural differentiation in mouse P19 cells.

First Author  Komori R Year  2013
Journal  PLoS One Volume  8
Issue  4 Pages  e61938
PubMed ID  23613978 Mgi Jnum  J:200642
Mgi Id  MGI:5508983 Doi  10.1371/journal.pone.0061938
Citation  Komori R, et al. (2013) Csn3 gene is regulated by all-trans retinoic acid during neural differentiation in mouse P19 cells. PLoS One 8(4):e61938
abstractText  kappa-Casein (CSN3) is known to play an essential role in controlling the stability of the milk micelles. We found that the expression of Csn3 was induced by all-trans retinoic acid (ATRA) during neural differentiation in P19 embryonal carcinoma cells from our study using DNA microarray. In this paper, we describe the detailed time course of Csn3 expression and the induction mechanism of Csn3 transcription activation in this process. The Csn3 expression was induced rapidly and transiently within 24 h of ATRA treatment. Retinoic acid receptor (RAR)-specific agonists were used in expression analysis to identify the RAR subtype involved upregulation of Csn3; a RARalpha-specific agonist mimicked the effects of ATRA on induction of Csn3 expression. Therefore, RARalpha may be the RAR subtype mediating the effects of ATRA on the induction of Csn3 gene transcription in this differentiation-promoting process of P19 cells. We found that the promoter region of Csn3 contained a typical consensus retinoic acid response element (RARE), and this RARE was necessary for ATRA-dependent transcriptional regulation. We confirmed that RARalpha bound to this RARE sequence in P19 cells. These findings indicated that the Csn3 expression is upregulated via ATRA-bound RARalpha and binding of this receptor to the RARE in the Csn3 promoter region. This will certainly serve as a first step forward unraveling the mysteries of induction of Csn3 in the process of neural differentiation.
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