Csn3 gene is regulated by all-trans retinoic acid during neural differentiation in mouse P19 cells.
Csn3 gene is regulated by all-trans retinoic acid during neural differentiation in mouse P19 cells.
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DOI：
10.1371/journal.pone.0061938
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Miyazawa H
中科院分区：
文献类型：
--
作者：
Komori R;Kobayashi T;Matsuo H;Kino K;Miyazawa H
已知κ-酪蛋白（CSN3）在控制乳胶束的稳定性中起重要作用。我们通过DNA芯片研究发现，在P19胚胎癌细胞神经分化过程中，全反式维甲酸（ATRA）诱导了Csn3的表达。本文详细描述了Csn3表达的时间过程，以及在此过程中Csn3转录激活的诱导机制。在ATRA处理的24 h内，Csn3的表达被快速而短暂地诱导。使用视黄酸受体（RAR）特异性激动剂进行表达分析，以确定与Csn3上调相关的RAR亚型；一种rar α特异性激动剂模拟了ATRA诱导Csn3表达的作用。因此，RARα可能是在P19细胞分化促进过程中介导ATRA诱导Csn3基因转录的RAR亚型。我们发现Csn3的启动子区域包含一个典型的共识维甲酸反应元件（RARE），该RARE对于atra依赖性转录调控是必需的。我们证实RARα在P19细胞中与这个RARE序列结合。这些发现表明，Csn3的表达通过atra结合的RARα和该受体与Csn3启动子区域的RARE结合而上调。这无疑是揭开神经分化过程中Csn3诱导之谜的第一步。
κ-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 RARα-specific agonist mimicked the effects of ATRA on induction of Csn3 expression. Therefore, RARα 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 RARα bound to this RARE sequence in P19 cells. These findings indicated that the Csn3 expression is upregulated via ATRA-bound RARα 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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影响因子：
2.7
作者：
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通讯作者：
CHAMBON, P
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