Expression of neuronal traits in pancreatic beta cells - Implication of neuron-restrictive silencing factor/repressor element silencing transcription factor, a neuron-restrictive silencer
Expression of neuronal traits in pancreatic beta cells - Implication of neuron-restrictive silencing factor/repressor element silencing transcription factor, a neuron-restrictive silencer
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DOI：
10.1074/jbc.272.3.1929
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发表时间：
1997-01-17
影响因子：
4.8
通讯作者：
Scharfmann, R
中科院分区：
文献类型：
--
作者：
Atouf, F;Czernichow, P;Scharfmann, R
胰腺β细胞（产生胰岛素的细胞）和神经元细胞有很多相似之处。在这里，我们调查是否相同的机制可以控制神经元和胰岛素分泌细胞中的神经元基因的表达。为此，我们测试了转录抑制因子神经元限制性沉默因子/抑制元件沉默转录因子（NRSF/REST）在胰岛素产生细胞中神经元基因表达中的作用。NRSF/REST是神经元命运的负调节因子。已知它可以沉默非神经元细胞中的神经元特异性基因。我们证明，与神经元嗜铬细胞瘤细胞系PC 12的情况一样，胰岛素瘤细胞系INS-1和其他三种产生胰岛素和胰高血糖素的细胞系中不存在编码NRSF/REST的mRNA。NRSF/REST活性也不存在于产生胰岛素的细胞系中。REST在胰岛素产生细胞系中的瞬时表达足以沉默含有NRSF/REST结合位点的报告基因，证明NRSF/REST在胰岛素产生细胞中神经元标记物表达中的作用。最后，通过寻找胰岛素分泌细胞中NRSF/REST调节基因的表达，我们增加了神经元和胰岛素分泌细胞中表达的基因列表。
Pancreatic beta cells (insulin-producing cells) and neuronal cells share a large number of similarities. Here, we investigate whether the same mechanisms could control the expression of neuronal genes in both neurons and insulin-producing cells. For that purpose, we tested the role of the transcriptional repressor neuron-restrictive silencing factor/repressor element silencing transciption factor (NRSF/REST) in the expression of a battery of neuronal genes in insulin-producing cells. NRSF/REST is a negative regulator of the neuronal fate. It is known to silence neuronal-specific genes in non-neuronal cells. We demonstrate that, as in the case of the neuronal pheochromocytoma cell line PC12, mRNA coding for NRSF/REST is absent from the insulinoma cell line INS-1 and from three other insulin and glucagon producing cell lines. NRSF/REST activity is also absent from insulin-producing cell lines. Transient expression of REST in insulin-producing cell lines is sufficient to silence a reporter gene containing a NRSF/REST binding site, demonstrating the role of NRSF/REST in the expression of neuronal markers in insulin-producing cells. Finally, by searching for the expression of NRSF/REST-regulated genes in insulin-producing cells, we increased the list of the genes expressed in both neurons and insulin-producing cells.