Organizational principles of the connexin-related brain transcriptome
Organizational principles of the connexin-related brain transcriptome
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DOI：
10.1007/s00232-007-9049-5
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发表时间：
2007-08-01
影响因子：
2.4
通讯作者：
Iacobas, Dumitru A.
中科院分区：
文献类型：
--
作者：
Spray, David C.;Iacobas, Dumitru A.
我们已经发现，编码缝隙连接蛋白Cx43、Cx32和Cx36的基因的缺失改变了小鼠大脑中大量基因的表达水平，这些基因位于所有的染色体上，编码所有主要功能类别的蛋白。Cx32和Cx43缺失脑中的基因调控比Cx36缺失脑中更相似，提示这两个基因对星形胶质细胞和少突胶质细胞都有转录调控的可能性。为了探索基因之间表达连锁的本质，我们研究了野生型和连接蛋白缺失脑中的协调表达模式。野生型脑中与Cx43的协同作用预测了Cx43缺失的调控，并具有相当高的准确性。此外，在Cx43缺失的大脑中，基因网络中的连锁受到了极大的干扰。这些发现提出了涉及缝隙连接基因的调控转录网络的几个原则，并提出了连接蛋白缺失表型的潜在原因以及调控机制的问题。
We have found that deletion of genes encoding the gap junction proteins Cx43, Cx32 and Cx36 alter the expression levels of large numbers of genes in mouse brain located on all chromosomes and encoding proteins from all major functional categories. Gene regulation in Cx32 and Cx43 null brains was more similar than that in the Cx36 null brain, suggesting the possibility of transcriptomic controls exerted by both genes on both astrocytes and oligodendrocytes. In order to explore the nature of expression linkage among the genes, we examined coordinated expression patterns in wild-type and connexin null brains. Coordination with Cx43 in wild-type brain predicted regulation in Cx43 nulls with considerable accuracy. Moreover, interlinkage within gene networks was greatly perturbed in the Cx43 null brain. These findings suggest several principles regarding regulatory transcriptomic networks involving gap junction genes and raise the issue of the underlying cause of connexin null phenotypes as well as mechanisms of regulation.