Overexpression of Stra13 a novel retinoic acid-inducible gene of the basic helix-loop-helix family, inhibits mesodermal and promotes neuronal differentiation of P19 cells
Overexpression of Stra13 a novel retinoic acid-inducible gene of the basic helix-loop-helix family, inhibits mesodermal and promotes neuronal differentiation of P19 cells
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DOI：
10.1101/gad.11.16.2052
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发表时间：
1997-08-15
影响因子：
10.5
通讯作者：
Chambon, P
中科院分区：
文献类型：
--
作者：
Boudjelal, M;Taneja, R;Chambon, P
我们报告了 Stra13 的 cDNA 克隆，这是一种来自 P19 胚胎癌细胞的新型视黄酸 (RA) 诱导基因，编码基本螺旋-环-螺旋 (bHLH) 蛋白，该蛋白与果蝇毛状蛋白和分裂和小鼠 Hes 蛋白的增强子显示出最高的序列相似性。 Stra13 不与 bHLH 蛋白的已知共有基序（E 盒和 N 盒）结合，但可以部分通过与基础转录机制的一般因子相互作用来抑制激活的转录（通过富含 or 螺旋的结构域）。在小鼠胚胎发生过程中，Stra13 RNA 在神经外胚层以及许多中胚层和内胚层衍生物中表达。值得注意的是，在野生型 P19 细胞仅进行中胚层/内胚层分化的条件下，P19 细胞中 Stra13 的过度表达会导致单层培养中的神经元分化。这种神经元分化伴随着中胚层和神经元标记物表达的改变，表明Stra13可能是最早的RA靶基因之一，当P19细胞聚集体暴露于RA时，其表达是抑制中胚层/内胚层分化和/或诱导神经元分化所必需的。我们的结果表明，Stra13 可能作为阻遏蛋白参与各种细胞谱系分化过程中发生的许多决策事件。
We report the cDNA cloning of Stra13, a novel retinoic acid (RA)-inducible gene from P19 embryonal carcinoma cells that encodes a basic helix-loop-helix (bHLH) protein that shows the highest sequence similarities to the Drosophila Hairy and Enhancer of split and mouse Hes proteins. Stra13 does not bind to the known consensus motifs (E-box and N-box) for bHLH proteins, but can repress activated transcription (through an or-helix rich domain) in part by interaction with general factors of the basal transcription machinery. During mouse embryogenesis, Stra13 RNA is expressed in the neuroectoderm, and also in a number of mesodermal and endodermal derivatives. Remarkably, overexpression of Stra13 in P19 cells results in neuronal differentiation in monolayer culture, under conditions where wild-type P19 cells only undergo mesodermal/endodermal differentiation. This neuronal differentiation is accompanied by an altered expression of mesodermal and neuronal markers, indicating that Stra13 could be one of the earliest RA target genes whose expression is required for repression of mesodermal/endodermal differentiation and/or induction of neuronal differentiation when P19 cell aggregates are exposed to RA. Our results raise the possibility that Stra13 could be involved as a repressor in a number of decision events occurring during differentiation of various cell lineages.