A new binding motif for the transcriptional repressor REST uncovers large gene networks devoted to neuronal functions
A new binding motif for the transcriptional repressor REST uncovers large gene networks devoted to neuronal functions
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DOI：
10.1523/jneurosci.0091-07.2007
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发表时间：
2007-06-20
影响因子：
5.3
通讯作者：
Mandel, Gail
中科院分区：
文献类型：
--
作者：
Otto, Stefanie J.;McCorkle, Sean R.;Mandel, Gail
阻遏元件1（RE1）沉默转录因子（REST）通过沉默非神经组织中的神经元基因来帮助维持神经组织的特性。此外，在肿瘤发生的上皮模型中，REST功能的丧失与黏附性的丧失相关，这表明编码这种特性的受REST调控的基因异常表达。到目前为止，尚未鉴定出受REST控制的黏附分子。在此，我们利用染色质占据的系列分析对肾细胞系中REST占据的靶序列（RE1位点）进行全基因组鉴定。我们发现了新的REST结合基序，并发现RE1位点的数量远远超过先前的估计。鉴定出了一大类编码黏附蛋白的靶标，以及编码神经内分泌肿瘤特征性蛋白的基因。出乎意料的是，被认为完全是非神经元的基因也包含一个RE1基序，并且在神经元中表达。这支持了REST结合是神经元表型的关键决定因素这一模型。
The repressor element 1 ( RE1) silencing transcription factor ( REST) helps preserve the identity of nervous tissue by silencing neuronal genes in non- neural tissues. Moreover, in an epithelial model of tumorigenesis, loss of REST function is associated with loss of adhesion, suggesting the aberrant expression of REST- controlled genes encoding this property. To date, no adhesion molecules under REST control have been identified. Here, we used serial analysis of chromatin occupancy to perform genome- wide identification of REST- occupied target sequences ( RE1 sites) in a kidney cell line. We discovered novel REST- binding motifs and found that the number of RE1 sites far exceeded previous estimates. A large family of targets encoding adhesion proteins was identified, as were genes encoding signature proteins of neuroendocrine tumors. Unexpectedly, genes considered exclusively non- neuronal also contained an RE1 motif and were expressed in neurons. This supports the model that REST binding is a critical determinant of neuronal phenotype.